Multi-parametric fluid determination systems using complex admittance

ABSTRACT

Apparatus, systems, and methods related to determining the identity and concentration of an intravenous fluid. The apparatus, systems, and methods described herein may provide near real-time monitoring and/or determination of the identity of the components of an intravenous fluid. The concentration and identify of all of the components of an intravenous fluid may be identified simultaneously.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a divisional of U.S. patent application Ser.No. 12/875,939, filed Sep. 3, 2010, Publication No. US-2011-0060198-A1,which is a continuation-in-part of International Application No.PCT/US2009/001494, filed Mar. 9, 2009, Publication No. WO 2009/114115which application claims priority to the following U.S. provisionalapplications: Application No. 61/035,339, filed Mar. 10, 2008;Application No. 61/049,367, filed Apr. 30, 2008; and Application No.61/198,523, filed Nov. 6, 2008, each of which is herein incorporated byreference in its entirety.

INCORPORATION BY REFERENCE

All publications and patent applications mentioned in this specificationare herein incorporated by reference in their entirety to the sameextent as if each individual publication or patent application wasspecifically and individually indicated to be incorporated by reference.

FIELD OF THE INVENTION

This application relates to the field of intravenous fluididentification and verification.

BACKGROUND OF THE INVENTION

The invention relates to intravenous fluid monitoring apparatus, systemsand methods. In particular, the invention relates to intravenous fluidmonitoring apparatus and systems comprising sensors for identifying oneor more components of an intravenous fluid, and to methods forintravenous delivery of fluid to a subject including sensing of thefluid during administration to the subject.

Intravenous fluid delivery systems and methods are known in the art.Such systems can generally comprise an intravenous infusion device(e.g., such as a cannula or a catheter) for infusion of fluid into thevasculature system of a subject in need thereof (e.g., a patient), oneor more fluid sources for containing an intravenous fluid or a componentthereof, and an fluid line assembly providing fluid communicationbetween the one or more fluid sources and the intravenous infusiondevice. Known systems include multiple arrangements and configurations,including, generally for example various systems (e.g., gravity-feedsystems; pump systems) for providing a motive force for delivery of thefluid from the source to the subject, as well as various furthercomponents typically integrated into the fluid line assembly such asconduits, fittings (e.g., Luer Lock™ fittings), backflow blocks, valves,and injection ports.

Some intravenous fluid delivery systems known in the art also includeone or more sensors, such as flow sensors (to measure a precise amountof a fluid being delivered), pressure sensors (e.g., to detect fluidline blockage) and/or ultrasonic sensors (e.g., to detect air-bubbles).See, for example, U.S. Patent Application Publication No. US2003/0159741 to Sparks.

Notwithstanding the various advances known in the art in connection withintravenous fluid delivery, there remains a need in the art forimprovements, especially improvements which enhance the accuracy and/orreliability of treatments involving intravenous fluid delivery topatients, and correspondingly which enhance patient safety. Inparticular, there remains a need for improvements in sensing, monitoringand recording the identity of fluid compositions (e.g., componentidentity, component concentration, component dose (e.g., current,projected) etc.) being delivered to patients in the course of treatment.

SUMMARY OF THE INVENTION

The present inventions provide apparatus, systems and methods related tointravenous fluid verification, identification and/or characterization.In particular, the apparatus, systems and methods herein relate tointravenous fluid characterization using complex admittance. Theapparatus, systems and methods of the invention are may be used formonitoring of intravenous fluids during administration to a subject. Asdescribed herein and in further detail below, the various inventionsoffer intravenous fluid monitoring approaches which are significantlyadvantaged over known systems, including for example by providing nearreal-time monitoring of the identity of one or more components of anintravenous fluid (e.g., the presence or absence of a component, thecomposition of a component, the concentration of a component, the time(absolute time or relative time versus other components) of infusion ofa component, the onset of component infusion (i.e., delivery through aninfusion device); the completion of component infusion, the componentdosing level (e.g., cumulative dosing level—current or projected),etc.). Such near real-time monitoring of intravenous fluids reduces thepotential for errors associated with intravenous administration, andespecially intravenous drug administration. Hence, the apparatus,systems and methods of the invention provide substantial advances inpatient safety. Such advances in safety can translate to a moremeaningful patient treatment experience, and to enhanced operationalefficiencies and reduced expenses for hospitals and other entities whichadminister fluids intravenously. Such inventions can applied, and suchadvantages can be realized in a number of various settings andapplications in which intravenous fluids are administered, including forexample, without limitation, at hospitals, clinics, surgical centers,homes (e.g., home hospice), nursing homes, assisted living environments,etc.

Generally, the apparatus, systems and methods of the invention aredirected to or effective for identifying one or more components of anintravenous fluid during administration of the fluid to a subject.Preferably, the apparatus, systems and methods of the invention aredirected to or effective for identifying one or more activepharmaceutical agents within an intravenous fluid during administrationof the fluid to a subject. Such active pharmaceutical agents caninclude, for example, an anticoagulant (e.g., heparin), ametabolically-active hormone (e.g., insulin), an anesthetic (e.g.,propofol), and/or an analgesic (e.g., morphine), among others.Additionally or alternatively, the apparatus, systems and methods of theinvention are directed to or effective for identifying one or more othercomponents of an intravenous fluid, preferably components used forhydration and ion metastasis of subjects.

Such components can preferably include, for example one or morecomponents selected from potassium chloride, sodium chloride, Ringer'slactate, and dextrose, in each case in molecular or ionic (e.g.,dissociated) form (e.g., sodium ion, potassium ion, chloride ion,calcium ion, lactate ion, and dextrose).

Generally, and preferably, the apparatus, systems and methods of theinvention are directed to or effective for identifying one or morecomponents of an intravenous fluid during administration of the fluid toa subject using a multi-parametric approach. In such approach, multipleparameters (e.g., multiple fluid properties such as without limitationrefractive index, electrochemical potential, impedance, admittance,conductivity, etc.) can be sensed, and the combination of parameters canbe correlated to obtain resolution of components within the fluid.Hence, an intravenous fluid can be sensed—for example with multiplesensors (or with a sensor having multiple sensor elements) and/or withmultiplexing of a sensor element to obtain independent sensingmeasurements—to generate a multi-parametric profile characteristic ofcomponent identity within the fluid. A multi-parametric profile can becorrelated to determine an identity of one or more components of thefluid. Such multi-parametric approaches advantageously provide forimproved resolution of components; therefore such approaches allow forimproved ability to distinguish between different fluid compositions,including for example the presence or absence of particular activepharmaceuticals, and/or various concentrations of a particular activepharmaceutical or other component. Multi-parametric approaches asdescribed herein are preferred, an can be generally used with anyaspects, embodiments and approaches described herein; however, manyaspects, embodiments and approaches of the invention do not requiremulti-parametric approaches and can be effected independently thereof.

Generally, and preferably, the apparatus, systems and methods of theinvention are directed to or effective for identifying one or morecomponents of an intravenous fluid during administration of the fluid toa subject using one or more sensors. The one or more sensors arepreferably selected to include at least one sensor other than a flowsensor, and/or in some embodiments also preferably other than a pressuresensor, and/or in some embodiments also preferably other than anultrasonic sensor. Generally for example, preferred sensors effectivewith the apparatus, systems and methods of the invention can include,without limitation, one or more sensors selected from an impedancesensor (e.g., an AC impedance spectroscopy sensor), an electrochemicalsensor (e.g., an electrochemical potential sensor), a thermal sensor(e.g., a thermal anemometer sensor), an optical sensor (e.g., arefractometer sensor, a transmission sensor, an absorbance sensor, aspectrometer (including a colorimeter) or, a turbidity sensor), arheological sensor (e.g., a viscometer), an electrical property sensor(e.g., a capacitor sensor, a pH sensor, a conductivity sensor, and aninductive sensor), and a fluid-displacing and/or fluid-shearing (e.g.,resonator) sensor. In various preferred embodiments, the sensors can beone or more sensors selected from an impedance sensor (e.g., an ACimpedance spectroscopy sensor) and an optical sensor (e.g., arefractometry sensor, a transmission sensor, an absorbance sensor, aspectrometer (including a colorimeter) or, a turbidity sensor). Incertain preferred embodiments, the apparatus, systems and methods of theinvention comprise or use at least two or more sensors or an integratedassembly comprising two or more sensors (e.g., an integrated assemblycomprising two or more sensor elements, each sensor element comprisingone or more sensing surfaces), and preferably such two or more sensorsbeing of different types and/or having different sensor approaches(e.g., impedance sensor, electrical property sensor, optical sensor,etc.). Preferably, such two or more sensors can include an impedancesensor (e.g., an AC impedance spectroscopy sensor), a thermal sensor,and/or an optical sensor (e.g., a refractometry sensor, a transmissionsensor, an absorbance sensor, a spectrometer (including a colorimeter)or, a turbidity sensor). Preferably, such two or more sensors can beintegrated into a common assembly, such as a common substrate, e.g., aspart of a common sensor subunit. For example, the apparatus, systems andmethods of the invention comprise an impedance sensor (e.g., an ACimpedance spectroscopy sensor) and an optical sensor (e.g., arefractometry sensor), each integral with and/or in a common sensorassembly such as a common substrate, or a common sensor subunit. Thevarious specific sensors and sensing approaches as described herein arepreferred, an can be generally used with any aspects, embodiments andapproaches described herein; however, many aspects, embodiments andapproaches of the invention do not require such certain specific sensorsor sensing techniques and can be effected independently thereof.

Generally, and preferably, the apparatus, systems and methods of theinvention are directed to or effective for identifying one or morecomponents of an intravenous fluid during administration of the fluid toa subject using a sensor having a sensor element (e.g., with a sensingsurface adapted for interaction with and being responsive to theintravenous fluid), where such sensor element (e.g., such sensingsurface) is positioned at a location within an intravenous fluid systemsuch that it interacts with the fluid (e.g., such sensing surfacecontacts the fluid) in relative proximity to the infusion location—thelocation at which the fluid enters a subject's vasculature system.Advantageously, monitoring of intravenous fluids proximal to theinfusion location (e.g., proximal to the distal end of a fluid lineassembly of an intravenous fluid delivery system, and/or proximal to aninfusion device of an intravenous fluid delivery system) can effectivelyreduce the potential for errors associated with intravenousadministration. Such proximity is less constrained by physical distance;rather it more generally refers to a location within an intravenousfluid delivery system at which the composition of the intravenous fluidis representative of (if not identical to) that which is delivered tothe subject. Hence, such proximity typically refers to a position orlocation within the intravenous fluid delivery system which isdownstream relative to various components of the intravenous fluiddelivery system which could change or otherwise effect the fluididentity (e.g., composition, concentration etc), including for exampledownstream of infusion valves, injection ports, supply line junctions,etc. In various embodiments of various aspects of the invention,therefore, the apparatus, systems and methods of the invention comprisea sensor element (e.g., having a sensor surface) positioned proximal to(e.g., at or near) the distal end of a fluid line assembly, and/orproximal to an infusion device. For example, such a sensor element caninclude a sensing surface in a cavity of an in-line housing, where thein-line housing optionally has inlet and outlet fittings (e.g., luerlocks), and can be integrated into the fluid line assembly upstream ofan infusion device. Alternatively, for example, such a sensor elementcan include a sensing surface in a cavity of a housing defined ininfusion device (e.g., catheter, needle, etc.). Further, in someembodiments, in addition to one or more sensors positioned formonitoring of intravenous fluids proximal to the infusion location(e.g., proximal to the distal end of a fluid line assembly and/orproximal to an infusion device), the apparatus, systems and method ofthe invention can also include an additional sensor positioned upstreamof an injection port—facilitating for example a differential measurementapproach. The approaches for positioning of the sensor element proximalto the infusion location, as described and as variously exemplifiedherein are preferred, and can be generally used with any aspects,embodiments and approaches described herein; however, many aspects,embodiments and approaches of the invention do not require such certainspecific positioning approaches and can be effected independentlythereof.

Generally, and preferably, the apparatus, systems and methods of theinvention are directed to or effective for identifying one or morecomponents of an intravenous fluid during administration of the fluid toa subject (e.g., a specific patient, for example at a hospital, clinic,surgical environment, home hospice, nursing home, assisted livingenvironment, etc), where such subject is positively and specificallyidentified in connection with monitoring and administration of theintravenous fluid. Various embodiments and aspects of the invention caninclude approaches for correlating the sensor data (i.e., data (e.g., asrepresented by a signal) originating from the sensor—either raw data ormore typically processed data) to a specific subject (e.g., patient).For example, the sensor (or apparatus or system comprising a sensor) caninclude an identifier circuit for correlating sensor data to a specificsubject. Typically, and preferably, such identifier circuit may be incommunication with one or more other circuits, including for examplecircuits for receiving processing, storing, displaying or transmittingdata, including data originating from the sensor element, such as asignal processing circuit or a data retrieval circuit. Such integratedpatient-identification approaches can further enhance the benefit topatient safety, by reducing the potential for errors associated withintravenous administration, and especially intravenous drugadministration. The various subject-identifier approaches as describedherein are preferred, an can be generally used with any aspects,embodiments and approaches described herein; however, many aspects,embodiments and approaches of the invention do not require such certainspecific subject-identifier approaches and can be effected independentlythereof.

Generally, and preferably, the apparatus, systems and methods of theinvention are directed to or effective for identifying one or morecomponents of an intravenous fluid during administration of the fluid toa subject with a remote and/or centralized monitoring approach. Althoughsuch remote and/or centralized monitoring approaches can be effected foran individual subject (e.g., in a home hospice environment), suchapproaches are especially advantageous in connection with multi-subjectcare environments. For example, different sensor data from one subjector from several different subjects (in each case, such sensor data beinglocally generated and specifically associated with an intravenous fluidbeing administered to a particular subject) can be acquired and/ormonitored at a location which is remote (relative to the patient)—suchas a nursing station; preferably such sensor data can be centrallymonitored at such remote location. In various aspects and embodimentstherefore, sensor data can be generated in a processor local to and incommunication with a sensor element (e.g., having a sensing element incontact with the intravenous fluid), preferably for each of two or moresubjects, and then such locally-generated sensor data stream(s) can beacquired by a processor remote from the sensor element. Such acquisitioncan be effected, for example, via wireless (e.g., WiFi, Bluetooth®,WiMax, IR, RF) or other communication approaches. The remote processorcan comprise one or more circuits for receiving, processing, storing,displaying or transmitting the acquired sensor data. The acquired sensordata can be monitored remotely, including for example at a centralmonitoring location. Preferably for example, the monitoring can be donevisually by human interaction with a display and/or can be furtherenhanced and effected by various automated approaches. In one suchautomated monitoring approach, a monitoring circuit can comprise a datacomparator module for comparing one or more parameters (e.g., datavalues) derived from sensor data with one or more parameters (e.g., datavalues) which are prescribed or proscribed for a particular subject(e.g. patient). Such patient-relevant parameters can betreatment-centric (e.g., applicable to all such patients undergoing aparticular treatment), including semi-customized treatment-centricparameters which include a patient-specific data input (e.g., a patientweight, patient age, etc.) to determine a treatment-centric parameter,and/or such patient-relevant parameters can be patient-centric (e.g.,wholly customized for a specific patient). Exemplary non-limitingparameters can include dosing levels, dosing timing (onset orcompletion), dosing frequency, etc. for various and specific activepharmaceutical agents or other components of an intravenous fluid.Patient-relevant parameters can be specific for the intravenousmonitoring system affected by the apparatus, systems and methods of theinvention, and/or can be common with (e.g., shared with) various othersystems, such as infusion pump systems (e.g., “smart pumps”). In oneembodiment, such infusion pump includes a control system with a datainput module, whereby patient-specific data (e.g., weight) can be usedto determine a patient relevant parameter used by both the pumpcontroller (as known in the art) and/or for use by the monitoringcircuit, e.g. a comparator module, of the present inventions forcomparison to a sensor-data parameter. In some embodiments, themonitoring circuit can share common circuitry with (or have the same orsimilar functionality and/or software as) a portion of the pumpcontroller circuit. Advantageously, the monitoring approaches of theapparatus, systems and methods of the invention can also include certainnotice (e.g., alarm) features—to provide notice to a caregiver that aspecific patient's intravenous fluid delivery system is operatingincongruous with a prescribed or proscribed treatment, and/or can alsoinclude certain corrective action (e.g., system control) features—tomake, preferably automated, a corrective action with the intravenousfluid delivery system. For example, upon determining an inconsistencybetween corresponding sensor-data-derived parameter and prescribed orproscribed patient-relevant parameter, an alarm can sound and/or acontrol circuit can activate a control element (e.g., an automatedinfusion valve) to make a change in the intravenous administrationregime. Such remote and/or central monitoring approaches can furtherenhance the benefit to patient safety, by reducing the potential forerrors associated with intravenous administration, and especiallyintravenous drug administration. The various remote and/or centralmonitoring approaches as described herein are preferred, an can begenerally used with any aspects, embodiments and approaches describedherein; however, many aspects, embodiments and approaches of theinvention do not require such remote and/or central monitoringapproaches and can be effected independently thereof.

Generally, and preferably, the apparatus, systems and methods of theinvention are directed to or effective for identifying one or morecomponents of an intravenous fluid during administration of the fluid toa subject with a sensor that comprises a processor (e.g., as includedwithin a processor assembly) which is physically separable from, andintermittently interfaceable with (e.g., for a finite, operationallyeffective period of time) a sensor element (e.g., as included within ahousing assembly). The approach of a temporally-limited engagement(interfacement) of the processor and the sensor element allows forregular operation while engaged/interfaced, and allows for physicalseparation of sensing function and processing function of a sensor (atleast for some period of time) after or between operations, with acorresponding separation of physical treatment of the embodiments whicheffect such function. For example, the sensor element can be physicallyseparated from the processor for a period of time to allow forsterilizing the sensor element (or a sensing surface thereof) or fordisposal and replacement of a (pre-)sterilized sensor element (or asensing surface thereof). Such separation also allows for re-use of theprocessor—for example, in connection with a second subsequent subject.Significantly, since processors are generally more expensive than sensorelements (or sensing surfaces thereof), the re-use of processors in sucha temporally-limited engagement (interfacing) approach provides forefficiency of capital investment, especially in a multi-subject (e.g.,hospital, surgical, nursing care, etc.) environment. The variousapproaches for temporally-limited/intermittent engagement/interfacing ofprocessor and sensor element as described herein are preferred, an canbe generally used with any aspects, embodiments and approaches describedherein; however, many aspects, embodiments and approaches of theinvention do not require such approaches fortemporally-limited/intermittent engagement/interfacing of processor andsensor element, and can be effected independently thereof.

Generally, and preferably, the apparatus, systems and methods of theinvention are directed to or effective for identifying one or morecomponents of an intravenous fluid during administration of the fluid toa subject with a sensor that comprises (i) an assembly comprising one ormore sensor elements, (ii) a signal-conditioning processor, includingone or more circuits adapted for conditioning (e.g., amplifying) asignal, and (iii) a signal-identification processor, including one ormore circuits adapted for identifying or determining a signalrepresentative of the identity of one or more components of anintravenous fluid (e.g. as corresponding to a component within acomposition or concentration of a component within a composition). Inone such preferred subembodiment, each of the assembly comprising theone or more sensor elements, the signal-conditioning processor, and thesignal-identification processor are each physically separate components.In an alternative of such preferred subembodiment, the assemblycomprising the one or more sensor elements is physically separate froman integrated assembly comprising the signal-conditioning processor andthe signal-identification processor. In another such preferredsubembodiment, an integrated assembly comprises each of the one or moresensor elements, the signal-conditioning processor, and thesignal-identification processor. Such various approaches for configuringthe sensor elements, the signal-conditioning processor and thesignal-identification processor are preferred, an can be generally usedwith any aspects, embodiments and approaches described herein; however,many aspects, embodiments and approaches of the invention do not requiresuch approaches for configuring these sensor components, and can beeffected independently thereof.

Various further aspects, embodiments and features of the inventions aredescribed herein throughout the specification and drawings; theaforementioned general summary is intended to be an introductory andnon-limiting summary of several commercially meaningful approachesincluded separately and in combination in various inventions. Generally,these various inventions enhance the accuracy and/or reliability oftreatments involving intravenous administration, thereby reducing riskof error in connection with such treatments, and improving patientsafety. The various inventions also enable improved effectiveness andefficiency of operations and improved efficiency of capital investment,especially in a multi-subject environment. The following more detailedsummary, and the subsequent detailed description and examples furtherdescribe the inventions.

In particular, in a first aspect, the invention is directed to apparatuscomprising a sensor (or a sensor subassembly) for identifying one ormore components of an intravenous fluid. In general, in this firstaspect of the invention the apparatus comprises one or more sensorelements having a sensing surface responsive to a fluid (e.g., to afluid property or a fluid composition). Preferably, the sensing surfaceof a sensor element is positioned for contact with the intravenousfluid. Alternatively, however, the sensing surface of a sensor elementcan be positioned for indirect, non-contact sensing of a fluid.Preferably, the sensing surface of a sensor element is positioned forcontact with the intravenous fluid during the administration of thefluid to the subject.

In a first general embodiment of the first aspect of the invention, theinvention is directed to an apparatus effective for multi-parametriccharacterization of one or more fluid components. Preferably, in thisfirst general embodiment, the apparatus comprises two or more sensorelements, each sensor element having a sensing surface positioned forcontact with the fluid. Preferably, in this first general embodiments,the two or more sensor elements can have a surface positioned in one ormore cavities of a housing. The housing can be adapted for fluidicinterface with a fluid line assembly of an intravenous fluid deliverysystem. For example, the housing can be adapted for in-line fluidcommunication with the fluid line assembly. Alternatively, the housingcan be defined or included in an intravenous infusion device (e.g., acatheter). The two or more sensor elements can be independent of eachother, including for example having physically separate sensingsurfaces, and/or for example having sensing surfaces which areindependently addressable (e.g., independently activated, independentlysampled, including for example simultaneously using differentiallyresolvable (deconvolutable) approaches or at different times). Inpreferred subembodiments of this first general embodiment, the apparatuscan comprise one or more signal processing circuits for (preferablyindependently) processing data originating from each of the two or moresensor elements, the processing circuits being configured to generate amulti-parametric profile characteristic of a component of the fluid.

In a second general embodiment of the first aspect of the invention, theinvention is directed to an apparatus effective for deploying sensorelements and sensor processors (e.g., including one or more circuits foractivating a sensor element or for receiving, processing, storing,displaying or transmitting data originating from the sensor element) ina capital efficient manner. Preferably, in this second generalembodiment, the apparatus comprises one or more sensor elements. Thesensor element(s) can have a sensing surface positioned for contact withthe fluid. Preferably, in this second general embodiment, the sensingsurface can be positioned in one or more cavities of a housing. Thehousing can be adapted for fluidic interface with a fluid line assemblyof an intravenous fluid delivery system. For example, the housing can beadapted for in-line fluid communication with the fluid line assembly.Alternatively, the housing can be defined or included in an intravenousinfusion device (e.g., a catheter). In any case, the apparatus in thissecond embodiment, can further comprise one or more contacts incommunication with (e.g., in electrical communication with) the sensingsurface of the sensor element(s). Such contacts are preferablyaccessible, to enable a communication interface with a sensor processor.The sensor processor can be in a processor assembly which contains theone or more circuits (as described herein above). The processor assemblycan further comprise one or more contacts in communication with the oneor more circuits. Such contacts are preferably accessible, forintermittent communication interface with the contacts of the sensingsurfaces. The intermittent interface of this general second embodimentof the first aspect of the invention allows for deployment of arelatively inexpensive housing assembly comprising the one or moresensor element(s), which housing assembly or sensor elements or sensingsurfaces thereof can be sterile or sterilizable for use, and/or whichcan be disposable after use. Such housing assembly or sensor elements orsensing surfaces can be deployed in practice with a reusable sensorprocessor (e.g., as a processor assembly), thereby providing for capitalefficiency. For example, a sensor processor can be interfaced with afirst housing assembly for use by a first subject, and followingthereafter, the same sensor processor can be interfaced with a secondhousing assembly for use by a second subject. Further related methodsand aspects are described below.

In a third general embodiment of the first aspect of the invention, theinvention is directed to an apparatus effective for ensuring andenhancing the reliability and/or accuracy of a patient-specifictreatment. Preferably, in this third general embodiment the apparatuscomprises one or more sensor elements. The sensor element(s) can have asensing surface positioned for contact with the fluid. Preferably, thesensing surface can be positioned in one or more cavities of a housing,as described above in connection with the second general embodiment ofthe first aspect of the invention. The apparatus can comprise a sensorprocessor. The sensor processor can include one or more circuits foractivating a sensor element or for receiving, processing, storing,displaying or transmitting data originating from the sensor element.Preferably, the apparatus can comprise one or more of a signalprocessing circuit and/or a data retrieval circuit. Preferably, theapparatus can further comprise an identifier circuit for correlatingsensor data to a specific patient. The identifier circuit is preferablyin communication with (e.g., electrical communication with) one or moreof a signal processing circuit and/or a data retrieval circuit. Theidentifier circuit can be used in operation to effectively monitorwhether a specific patient is receiving an intravenous fluid consistentwith a prescribed or proscribed treatment plan.

In a fourth general embodiment of the first aspect of the invention, theinvention is directed to an apparatus effective for deploying afluid-component sensor into in intravenous delivery system. Preferably,in this fourth general embodiment of the first aspect of the invention,the apparatus comprises an infusion device for infusion of fluid intothe vasculature system of a subject, and one or more sensor elementsintegral with the infusion device. The sensor element(s) can have asensing surface positioned for contact with the fluid. Preferably, thesensing surface can be positioned in one or more cavities (e.g., of ahousing) defined in the infusion device.

The first, second, third and fourth general embodiments of the firstaspect of the invention can be effected in combination with each other.The first, second, third and fourth general embodiments of the firstaspect of the invention can be effected and/or used as well with eachgeneral embodiment of the second and third aspects of the invention.Various specific subembodiments of each general embodiments of the firstaspect of the invention are also applicable with specific subembodimentsof general embodiments of the second and third aspects of the invention.

In a second aspect, the invention is directed to systems for intravenousdelivery of fluids into a subject in need thereof (e.g., a patient). Ingeneral, in this second aspect of the invention the system comprises afluid line assembly and one or more sensor elements. The fluid lineassembly can generally include one or more conduits and/or othercomponents. The fluid line assembly can have a first end adapted forfluid communication with a fluid source and a second distal end adaptedfor fluid communication with an intravenous infusion device for infusionof fluid into the vascular system of the subject (e.g., a patient). Thesensor element(s) can have a sensing surface positioned for contact withthe fluid. Preferably, in this first general embodiment of the secondaspect of the invention, the sensing surface can be positioned in one ormore cavities of a housing. The housing can be adapted for fluidicinterface with a fluid line assembly of an intravenous fluid deliverysystem. For example, the housing can be adapted for in-line fluidcommunication with the fluid line assembly. Alternatively, the housingcan be defined or included in an intravenous infusion device (e.g., acatheter).

In a first general embodiment of the second aspect of the invention, theinvention is directed to a system for intravenous fluid delivery to apatient comprising a fluid line assembly and an apparatus of the firstaspect of the invention.

In a second general embodiment of the second aspect of the invention,the invention is directed to a system for intravenous fluid delivery toa patient comprising a fluid line assembly having a first end adaptedfor fluid communication with a fluid source and a second distal endadapted for fluid communication with an intravenous infusion device forinfusion of fluid into the vascular system of the subject (e.g., apatient). The system further comprises a sensor element having a sensingsurface proximate to the second distal end of the fluid line assembly.The sensing surface can be positioned in one or more cavities of ahousing. The housing can be adapted for fluidic interface with a fluidline assembly proximate to its distal end. For example, the housing canbe adapted for in-line fluid communication with the fluid line assemblyproximate to its distal end. Alternatively, the housing can be definedor included in an intravenous infusion device (e.g., a cannula or acatheter). The system can further comprise one or more injection portsand one or more additional sensor elements for one or more additionalsensors, such additional sensor elements being positioned upstream ofthe injection port—facilitating for example a differential measurementapproach.

In a third general embodiment of the second aspect of the invention, theinvention is directed to a system for intravenous fluid delivery to asubject which includes a remote processor, effective for example formonitoring sensor data from one or from multiple local sensors (e.g.,for remote monitoring of a corresponding multiple subjects). The remoteprocessor can therefore comprise a data acquisition circuit foracquiring sensor data originating from one or more local sensors (e.g.,via a corresponding one or more local processors), and a monitoringcircuit for monitoring the sensor data. The system can include a localprocessor comprising one or more circuits for activating a sensorelement or for receiving, processing, storing, displaying ortransmitting data originating from the sensor element. Preferably, theapparatus can comprise one or more of a signal processing circuit and/ora data retrieval circuit. Preferably, the system can further comprise anidentifier circuit for correlating sensor data to a specific patient.The local processor can be proximate to and in communication with one ormore sensing surfaces of a sensor element. The sensor element can have asensing surface positioned to contact the fluid during administration tothe subject, as described.

In a further, fourth general embodiment of the second aspect of theinvention, the invention is directed to a system for intravenous fluiddelivery to a subject comprising a fluid line assembly and a sensor foridentifying one or more active pharmaceutical agents within the fluid.The sensor can comprise a sensor element having a sensing surfacepositioned for contact with the fluid, and one or more circuits incommunication with the sensor element for activating the sensor elementor for receiving, processing, storing, displaying or transmitting dataoriginating from the sensor element. The sensor is configured todistinguishably detect one or more active pharmaceutical agents.Preferably, the sensor is configured to identify one or more activepharmaceutical agents selected from the group consisting of ananticoagulant (e.g., heparin), a metabolically-active hormone (e.g.,insulin), an anesthetic (e.g., propofol), and an analgesic (e.g.,morphine).

In another, fifth general embodiment of the second aspect of theinvention, the invention is directed to a system for intravenous fluiddelivery to a subject comprising a fluid line assembly and a sensor foridentifying one or more components of the fluid. The sensor can comprisea sensor element having a sensing surface positioned for contact withthe fluid, and one or more circuits in communication with the sensorelement for activating the sensor element or for receiving, processing,storing, displaying or transmitting data originating from the sensorelement. The sensor is configured to distinguishably detect one or morecomponents of the fluid. Preferably, the sensor is configured toidentify one or more components of the fluid selected from the groupconsisting of a metal ion, halide ion, organic ion or salts, and asugar, preferably for example sodium ion, potassium ion, chloride ion,calcium ion, magnesium ion, lactate ion, and dextrose. For example, suchions can be components in fluid compositions comprising potassiumchloride, sodium chloride, Ringer's lactate, and dextrose. Preferably,the method comprises sensing the fluid to identify potassium chloride,potassium ion or chloride ion.

In a sixth general embodiment of the second aspect of the invention, theinvention is directed to a system for intravenous fluid delivery to asubject comprising a fluid line assembly and a sensor other than a flowsensor, the sensor comprising a sensor element having a sensing surfacepositioned for contact with the fluid. The sensor can preferably furthercomprise one or more circuits in communication with the sensor elementfor activating the sensor element or for receiving, processing, storing,displaying or transmitting data originating from the sensor element.

The first, second, third, fourth, fifth and sixth general embodiments ofthe second aspect of the invention can be effected in combination witheach other. The first, second, third, fourth, fifth and sixth generalembodiments of the second aspect of the invention can be effected and/orused as well with each general embodiment of the first and third aspectsof the invention. Various specific subembodiments of each generalembodiments of the second aspect of the invention are also applicablewith specific subembodiments of general embodiments of the first andthird aspects of the invention.

In a third aspect, the invention is directed to methods for intravenousdelivery of fluid to a subject in need thereof (e.g., a patient). Ingeneral, such methods comprise administering an intravenous fluid to asubject in need thereof and sensing the fluid, preferably to identifyone or more components thereof.

In a first general embodiment of the third aspect of the invention, theinvention is directed to a method for intravenous delivery of fluid to asubject in need thereof. The method comprises administering the fluid tothe subject, and sensing the fluid with an apparatus of the first aspectof the invention or with a system of the second aspect of the invention.Preferably, the method further comprises identifying one or morecomponents of the fluid during administration of fluid to the subject.

In a second general embodiment of the third aspect of the invention, theinvention is directed to a method for intravenous delivery of fluid to asubject in need thereof. The method comprises administering the fluid tothe subject, sensing the fluid to generate a multi-parametric profilecharacteristic of a component of the fluid, and identifying one or morecomponents of the fluid during administration of fluid to the subjectbased on the multi-parametric profile. In preferred subembodiments,sensing the fluid comprises exposing a sensing surface of a first sensorelement to the fluid, exposing a sensing surface of a second sensorelement to the fluid, and independently processing data originating fromeach of the first sensor element and the second sensor element togenerate the multi-parametric profile.

In a third general embodiment of the third aspect of the invention, theinvention is directed to a method for intravenous delivery of fluid to asubject in need thereof. The method comprises administering a firstfluid to a first subject, exposing a sensing surface of a first sensorelement to the first fluid, interfacing (e.g., communicatively engaging)a processor with the first sensor element and identifying one or morecomponents of the first fluid during administration thereof to the firstsubject. The processor can comprise one or more circuits for activatinga sensor element or for receiving, processing, storing, displaying ortransmitting data originating from the a sensor element. The methodfurther comprises dis-interfacing (e.g., communicatingly disengaging)the processor from the first sensor element. The method furthercomprises administering a second fluid to a second subject, exposing asensing surface of a second sensor element to the second fluid, andinterfacing the (same) processor with the second sensor element andidentifying one or more components of the second fluid duringadministration thereof to the second subject. This method preferably, ina subembodiment, can further comprise disposing or sterilizing thesensing surface of each of the first sensor element and the secondsensor element after administration of fluid to the respective subject.

In a fourth general embodiment of the third aspect of the invention, theinvention is directed to a method for intravenous delivery of fluid to asubject in need thereof. The method comprises administering the fluid tothe subject, sensing the fluid to generate sensor data for identifyingone or more components of the fluid during administration of fluid tothe subject, and correlating the sensor data to the specific subject.Preferably, this method can further comprise deriving one or moreparameters from the sensor data, and comparing the one or moresensor-derived parameters with one or more prescribed or proscribedpatient-relevant parameters.

In a fifth general embodiment of the third aspect of the invention, theinvention is directed to a method for intravenous delivery of fluid to asubject in need thereof. The method comprises administering the fluid tothe subject through an intravenous infusion device, and sensing thefluid with a sensing surface of a sensor element, where the sensingsurface is positioned proximate to the intravenous infusion device toidentify one or more components of the fluid during administration offluid to the subject. Preferably in this method, fluid is exposed to asensing surface of a sensor element, with the sensing surface beingpositioned within a cavity of a housing adapted for in-line fluidcommunication of a fluid line assembly. Preferably in this method, suchan in-line housing is positioned directionally adjacent to the subjectrelative to the position of any fluid source supply line or anyinjection port of the fluid line assembly. Alternatively for thismethod, fluid is exposed to a sensing surface of a sensor element, andthe sensing surface being positioned within a cavity of a housingdefined in the intravenous infusion device.

In a sixth general embodiment of the third aspect of the invention, theinvention is directed to a method for intravenous delivery of fluid to asubject in need thereof. The method comprises administering the fluid tothe subject, sensing the fluid with a sensor element having a sensingsurface exposed to the fluid during administration of fluid to thesubject, generating sensor data in a processor local to and incommunication with the sensor element, the local processor optionallycomprising one or more circuits for activating a sensor element, thelocal processor comprising one or more circuits for receiving,processing, storing, displaying or transmitting data originating fromthe sensor element. The method further comprises acquiring the sensordata at a processor remote from the sensor element. The remote processorcan comprise one or more circuits for receiving, processing, storing,displaying or transmitting the acquired sensor data. The method furthercomprises monitoring the acquired sensor data or data derived therefrom.

In a seventh general embodiment of the third aspect of the invention,the invention is directed to a method for intravenous delivery of fluidto two or more subjects in need thereof. The method comprisesadministering a first fluid to a first subject, sensing the first fluidwith a first sensor element having a sensing surface exposed to thefirst fluid during administration of fluid to the first subject, andgenerating sensor data in a first processor local to and incommunication with the first sensor element. The method furthercomprises administering a second fluid to a second subject, sensing thesecond fluid with a second sensor element having a sensing surfaceexposed to the second fluid during administration of fluid to the secondsubject, and generating sensor data in a second processor local to andin communication with the second sensor element. The method can furtherinclude acquiring the sensor data from each of the first local processorand the second local processor at a processor remote from each of thefirst sensor element and the second sensor element, and monitoring theacquired sensor data from each of the first local processor and thesecond local processor or monitoring data derived therefrom.

In an eighth general embodiment of the third aspect of the invention,the invention is directed to a method for intravenous delivery of fluidto two or more subjects in need thereof. The method comprisesadministering the fluid to the subject, and sensing the fluid toidentify one or more active pharmaceutical agents within fluid duringadministration of fluid to the subject. Preferably, the method of thiseighth general embodiment comprises sensing the fluid to identify one ormore active pharmaceutical agents selected from the group consisting of:an anticoagulant (e.g., heparin), a metabolically-active hormone (e.g.,insulin), an anesthetic (e.g., propofol), and an analgesic (e.g.,morphine).

In a ninth general embodiment of the third aspect of the invention, theinvention is directed to a method for intravenous delivery of fluid totwo or more subjects in need thereof. The method comprises administeringthe fluid to the subject, sensing the fluid to identify one or morecomponents within fluid during administration of fluid to the subject,the one or more components being selected from the group consisting of ametal ion, halide ion, organic ion or salts, and a sugar, preferably forexample sodium ion, potassium ion, chloride ion, calcium ion, magnesiumion, lactate ion, and dextrose. For example, such ions can be componentsin fluid compositions comprising potassium chloride, sodium chloride,Ringer's lactate, and dextrose. Preferably, the method comprises sensingthe fluid to identify potassium chloride, potassium ion or chloride ion.

The first, second, third, fourth, fifth, sixth, seventh, eighth andninth general embodiments of the third aspect of the invention can beeffected in combination with each other. The first, second, third,fourth, fifth, sixth, seventh, eighth and ninth general embodiments ofthe third aspect of the invention can be effected and/or used as wellwith each general embodiment of the first and second aspects of theinvention. Various specific subembodiments of each general embodimentsof the third aspect of the invention are also applicable with specificsubembodiments of general embodiments of the first and second aspects ofthe invention.

Various embodiments of the invention as described above and hereinafterinclude listings of groups of alternatives (e.g., Markush groups); ineach case, any such listing is intended to disclose each such member ofthe group collectively as well as individually.

Various features of the invention, including features defining each ofthe various aspects of the invention, including general and preferredembodiments thereof, can be used in various combinations andpermutations with other features of the invention. Features andadvantages are described herein, and will be apparent from the drawingsand the following detailed description.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1(A-C) illustrate schematic representations of intravenous fluiddelivery systems, including a contextual schematic illustration showinggeneral features (FIG. 1A), and more detailed schematic illustrationsshowing further features thereof (FIG. 1B, FIG. 1C).

FIG. 2 illustrates a schematic representation of an embodiment of anapparatus comprising a sensor element having a sensing surfaceintegrated into an in-line housing adapted for fluidic interface with afluid line assembly.

FIG. 3(A-C) illustrate schematic representations of an embodiment of anapparatus comprising a sensor element having a sensing surfaceintegrated into an intravenous infusion device (e.g., catheter) adaptedfor fluid communication with fluid line assembly, including aperspective view (FIG. 3A), side cut-away elevation (FIG. 3B), anddetail of the sensor element containing portion thereof (FIG. 3C).

FIG. 4 illustrates a schematic representation of a multi-parametricapproach for identifying one or more components of the intravenousfluid.

FIG. 5(A-E) illustrate schematic representations of various circuitsassociated with sensors of various aspects and embodiments of theinventions, including independently: a block diagram of a specificpreferred circuit configuration (FIG. 5A); a high-level schematicdiagram showing a sensor element configured in an assembly such as ahousing assembly, and various circuits being configured in an assemblysuch as housing assembly, and/or in a local processor and/or in a remoteprocessor (FIG. 5B); and additional high-level schematic diagramsshowing alternative configurations for a system comprising (i) a (one ormore) sensor element, (ii) a signal-conditioning processor, includingone or more circuits adapted for conditioning (e.g., amplifying) asignal, and (iii) a signal-identification processor, including one ormore circuits adapted for identifying or determining a signalrepresentative of the identity of one or more components of anintravenous fluid (e.g. as corresponding to a component within acomposition or concentration of a component within a composition) (FIGS.5C through 5E).

FIG. 6 (A-G) illustrate schematic representations of various sensors,including an optic fiber refractive index sensor (FIG. 6A), anelectrochemical potential sensor (FIG. 6B), and various schematic viewsof an integrated assembly comprising impedance and refractive indexsensor elements (FIG. 6C through FIG. 6G), including a perspective viewof the integrated sensor element assembly (FIG. 6C), a top-plan view ofa first surface of a first substrate thereof (FIG. 6D), a detail of thesensing surfaces of the impedance sensor elements as shown therein (FIG.6E), a perspective assembly view of the first substrate and a secondsubstrate, shown with a functional communication port, such as a USBport (FIG. 6F), and a perspective view of the (assembled) integratedassembly of impedance/refractive index sensor elements (FIG. 6G).

FIG. 7 (A-D) illustrate various data derived from Example 2, includingplots of measurements of admittance, real portion (FIG. 7A), admittance,imaginary portion (FIG. 7B), optical refractive index (FIG. 7C), and amulti-parametric representation of such measurements (FIG. 7D).

FIG. 8 (A-D) illustrate various data derived from Example 3, includingplots of measurements of admittance, real portion (FIG. 8A), admittance,imaginary portion (FIG. 8B), optical refractive index (FIG. 8C), and amulti-parametric representation of such measurements (FIG. 8D).

FIG. 9 (A-B) illustrate various data derived from Example 4, includingplots of measurements of out-of-phase current (y-axis) and in-phasecurrent (x-axis) for injections of potassium chloride (KCl) andmagnesium sulfate (MgSO4) (FIG. 9A), as well as for subsequentinjections with water.

Various aspects of the figures are described in further detail below, inconnection with the detailed description.

DETAILED DESCRIPTION OF THE INVENTION

The present inventions provide apparatus, systems and methods related tointravenous fluid administration. The apparatus, systems and methods ofthe invention are more specifically related to monitoring of intravenousfluids during administration to a subject.

Generally, as summarized above and described in further detail below,the apparatus, systems and methods of the invention are directed to oreffective for identifying one or more components of an intravenous fluidduring administration of the fluid to a subject. Preferably, theapparatus, systems and methods of the invention are directed to oreffective for identifying one or more active pharmaceutical agentswithin an intravenous fluid during administration of the fluid to asubject. Other components can also be detected, especially componentsrelevant to hydration and/or ion metastasis (e.g., electrolyte balance)and/or vasculature pressure of patients. The one or more components ofan intravenous fluid can preferably be identified during administrationof the fluid to a subject using a multi-parametric approach. Manyspecific sensors known in the art can be used in connection with thevarious aspects and embodiments of the invention. Preferred sensorsinclude one or more sensors selected from an impedance sensor (e.g., anAC impedance spectroscopy sensor), an electrochemical sensor (e.g., anelectrochemical potential sensor), a thermal sensor (e.g., a thermalanemometer sensor), an optical sensor (e.g., a refractometry sensor, atransmission sensor, an absorbance sensor, a spectrometer (including acolorimeter), a turbidity sensor), a Theological sensor (e.g., aviscometer), an electrical property sensor (e.g., a capacitor sensor, apH sensor, a conductivity sensor, and an inductive sensor), and afluid-displacing or fluid-shearing (e.g., resonator) sensor. Preferably,a system comprises two or more sensors, for example an integratedassembly comprising two or more sensor elements, each comprising one ormore sensing surfaces (e.g., an impedance sensor and an optical (e.g.,refractive index) sensor). Preferably, a sensor having a sensor element(e.g., with a sensing surface adapted for interaction with and beingresponsive to the intravenous fluid) is positioned such that the sensorelement (e.g., the sensing surface) within an intravenous fluid systemsuch that it interacts with the fluid (e.g., such sensing surfacecontacts the fluid) in relative proximity to the infusion location—thelocation at which the fluid enters a subject's vasculature system, e.g.,proximal to the distal end of the fluid line assembly or proximal to theintravenous infusion device. Preferably, the apparatus, systems andmethod of the invention provide for the subject being positively andspecifically identified in connection with monitoring and administrationof the intravenous fluid; hence, for example, the sensor (or apparatusor system comprising a sensor) can include an identifier circuit forcorrelating sensor data to a specific subject. Preferably, the systemsare effected with a remote and/or centralized monitoring approach. Forexample, different sensor data from one subject or from severaldifferent subjects (in each case, such sensor data being locallygenerated and specifically associated with an intravenous fluid beingadministered to a particular subject) can be acquired and/or monitoredat a location which is remote (relative to the patient)—such as anursing station; preferably such sensor data can be centrally monitoredat such remote location. For example and without limitation, monitoringcan be visual by human interaction with a display and/or can be furtherenhanced and effected by various automated approaches, includingautomated approaches involving notice to caregivers (alarms, emails,text message) and/or specific corrective or subsequently prescribedactions within the system. In preferred embodiments of various aspectsof the invention, the sensor can comprise a processor which isphysically separable from, and conversely, intermittently interfaceablewith a sensor element. Such temporally-limited engagement(interfacement) of processor and sensor element allows for anoperational period (while engaged/interfaced) and a non-operationalperiod (with physical separation of sensor element from the processor).The non-operational period can allow for sterilizing the sensor element(or a sensing surface thereof) or for disposal and replacement of a(pre-)sterilized sensor element (or a sensing surface thereof). Theprocessor can be re-used, for example, in connection with a secondsubject, either in the same location (a later subject) or in a differentlocation (e.g., multiplexing the same processor over various subjects).In preferred embodiments of various aspects of the invention, the sensorcan comprise: an assembly comprising one or more sensor elements; asignal-conditioning processor, including one or more circuits adaptedfor conditioning (e.g., amplifying) a signal; and asignal-identification processor, including one or more circuits adaptedfor identifying or determining a signal representative of the identityof one or more components of an intravenous fluid. The variousaforementioned attributes and features of the inventions can be used ineach of the various possible combinations and permutations with eachother, as applicable.

As described herein and in further detail below, the various inventionsoffer intravenous fluid monitoring approaches which are significantlyadvantaged over known systems, including for example by providing nearreal-time monitoring of the identity of one or more components of anintravenous fluid (e.g., the presence or absence of a component, thecomposition of a component, the concentration of a component, the timeof infusion (absolute time or relative time versus other components),the onset of component delivery; the completion of component infusion,the cumulative dosing level (e.g., current or projected) of a componentbeing delivered, etc.). Such near real-time monitoring of intravenousfluids reduces the potential for errors associated with intravenousadministration, and especially intravenous drug administration. Hence,the apparatus, systems and methods of the invention provide substantialadvances in patient safety. Such advances in safety can translate to amore meaningful patient treatment experience, and to enhancedoperational efficiencies and reduced expenses for hospitals and otherentities which administer fluids intravenously. Such inventions canapplied, and such advantages can be realized in a number of varioussettings and applications in which intravenous fluids are administered,including for example, without limitation, at hospitals, clinics,surgical centers, homes (e.g., home hospice), nursing homes, assistedliving environments, etc.

Intravenous Fluid Delivery Systems

Generally, an intravenous fluid delivery system of the invention caninclude various systems known in the art or later developed whichprovide for delivery of fluids to the vasculature system of a subject inneed thereof. Generally, such systems can be intermittent or continuous(e.g., including intravenous drip systems). With reference to FIGS. 1Athrough 1C, in operation intravenous fluid delivery systems generallycomprise an intravenous fluid source 100 in fluid communication with anintravenous infusion device 300 through a fluid line assembly 200. Theintravenous infusion device 300 is adapted for infusion of fluid intothe vasculature system (e.g., a vein) of a subject 10. With furtherreference to FIG. 2 and FIGS. 3A through 3C, the intravenous fluiddelivery systems of the invention can comprise a sensor 500 comprisingone or more sensor elements 502 having a sensing surface 504. Thesensing surface 504 can be in communication (e.g., electricalcommunication via electrical connector 506) to one or more contacts508).

Various intravenous fluid delivery system configurations can beemployed, and various such intravenous infusion devices can be employed.For example, the intravenous fluid delivery system can be configured forperipheral intravenous infusion, for central intravenous infusion, orfor peripherally-inserted central intravenous infusion. The system canbe adapted for various infusion profiles and approaches; for example,infusion can be rapid, can be drip, can be continuous or can beintermittent.

Various suitable intravenous infusion device can be used in connectionwith the invention. Preferably, as shown in the FIGS. 1A through 1C,such intravenous infusion devices 300 can be integrated with or in fluidcommunication with a fluid line assembly 200 and/or a fluid source 100.Generally, and with reference to FIGS. 3A through 3C, such anintravenous infusion device 300 (e.g., a catheter) can comprise a firstend 310 adapted for fluid communication with a fluid line assembly, asecond distal end 320 adapted for insertion through the skin into thevasculature system of the subject, preferably through a peripheral vein,and a housing 330 (e.g., a catheter hub), providing excorporalstructural support and having a cavity 340 providing fluid communicationbetween the first end 310 and the second distal end 320 of the infusiondevice. The intravenous infusion device 300 can also include a supportelement 390 (e.g., such as adhesive wings) for supporting the device 300during administration of fluid to a subject. Other intravenous infusiondevices can also be used in connection with aspects and embodiments ofthe inventions. Such devices can include for example an integrated fluidsource—for example, a needle-type infusion device (e.g., comprising asyringe a needle in fluid communication with the syringe). Such devicescan also include ported cannulae having an injection port on a first endand a second distal end adapted for insertion through the skin into thevasculature system of the subject. The intravenous infusion device canalso include an implantable infusion device such as an implantable port.The port can be, for example, a central venous line comprising a cavitycovered with a pliable sealant as a cavity cover (e.g., silicone rubber)and adapted for being implanted under the skin. A fluid can beadministered through such implantable port intermittently by placing asmall needle or catheter through the skin, piercing the silicone, andadministering the fluid into the cavity. The cavity cover can resealafter withdrawal of the needle or catheter.

Other system components can include, for example in a typicalintravenous fluid delivery system, one or more sterile containers (glassbottle, plastic bottle or plastic bag) adapted for containing (orpre-filled to contain) fluids, typically configured with an attacheddrip chamber. The system can comprise a fluid line assembly comprisingone or more conduit sections (e.g., each conduit for example comprisinga long sterile tube), optionally configured with a clamp to regulate orstop the flow, various connectors, one or more infusion pumps, adaptedfor providing control over the flow rate and total amount of fluiddelivered.

Pharmaceutical Agents, Other Components and Preferred Sensors

Generally, the apparatus, systems and methods of the invention aredirected to or effective for identifying one or more components of anintravenous fluid during administration of the fluid to a subject. Theintravenous fluid is not narrowly critical and can be of various types,including generally for example crystalloid solutions and colloidsolutions. Crystalloid solutions can comprise aqueous solutions ofmineral salts or other water-soluble molecules, including activepharmaceutical agents. Colloids can comprise larger semi-soluble orinsoluble molecules, including active pharmaceutical agents. Generally,the intravenous fluids are sterile fluids.

Preferably, the apparatus, systems and methods of the invention aredirected to or effective for identifying one or more activepharmaceutical agents within an intravenous fluid during administrationof the fluid to a subject. Such active pharmaceutical agents caninclude, for example, an anticoagulant (e.g., heparin), ametabolically-active hormone (e.g., insulin), an anesthetic (e.g.,propofol), and/or an analgesic (e.g., morphine), among others. Variousone or more sensors are configured for sensing a property of a fluidwhich can be correlated to identify an active pharmaceutical agentcomponent of the fluid. For example, the sensor can comprise one or moresensor elements having a sensing surface positioned for contact with thefluid, and one or more circuits in communication with the sensor elementfor activating the sensor element or for receiving, processing, storing,displaying or transmitting data originating from the sensor element. Thesensor can be configured to distinguishably detect one or more activepharmaceutical agents. Preferably, the sensor is configured to identifyone or more active pharmaceutical agents selected from the groupconsisting of an anticoagulant (e.g., heparin), a metabolically-activehormone (e.g., insulin), an anesthetic (e.g., propofol), and ananalgesic (e.g., morphine).

Additionally or alternatively, the apparatus, systems and methods of theinvention are directed to or effective for identifying one or more othercomponents of an intravenous fluid, preferably components used forhydration and ion metastasis of subjects. Such components can preferablyinclude, for example one or more components selected from potassiumchloride, sodium chloride, Ringer's lactate, and dextrose, in each casein molecular or ionic (e.g., dissociated) form (e.g., sodium ion,potassium ion, chloride ion, calcium ion, lactate ion, and dextrose).The sensor can comprise a sensor element having a sensing surfacepositioned for contact with the fluid, and one or more circuits incommunication with the sensor element for activating the sensor elementor for receiving, processing, storing, displaying or transmitting dataoriginating from the sensor element. The sensor can be configured todistinguishably detect one or more components of the fluid. Preferably,the sensor is configured to identify one or more components of the fluidselected from the group consisting of a metal ion, halide ion, organicion or salts, and a sugar, preferably for example sodium ion, potassiumion, chloride ion, calcium ion, magnesium ion, lactate ion, anddextrose. For example, such ions can be components in fluid compositionscomprising potassium chloride, sodium chloride, Ringer's lactate, anddextrose. Preferably, the method comprises sensing the fluid to identifypotassium chloride, potassium ion or chloride ion.

Typical intravenous fluids can comprise normal saline, preferably forexample a solution of sodium chloride at 0.9% concentration, which isclose to the concentration in the blood (isotonic). The intravenousfluid can comprise Ringer's lactate or Ringer's acetate, anotherisotonic solution. In some instances, the intravenous fluid can comprisea sugar such as dextrose, for example a solution of 5% dextrose inwater, sometimes referred to as D5W. The selection of a particularcarrier fluid may also depend on the chemical properties of the activepharmaceutical agents being administered.

Table I shows compositions of common intravenous fluids used inconnection with intravenous fluid delivery systems.

TABLE I Composition of Intravenous Fluid Solutions [Na+] [Cl] [Glucose][Glucose] Solution Other Name (mmol/L) (mmol/L) (mmol/L) (mg/dl) DW5 5%Dextrose 0 0 278 5000 2/3D & 3.3% Dex- 51 51 185 3333 1/3S trose/0.3%saline Half-nor- 0.45% NaCl 77 77 0 0 mal saline Normal 0.9% NaCl 154154 0 0 saline Ringer's Lactated 130 109 0 0 lactate RingerRinger's lactate also typically can have, for example and withoutlimitation 28 mmol/L lactate, 4 mmol/L K+ and 3 mmol/L Ca2+.

Generally, and preferably, the apparatus, systems and methods of theinvention are directed to or effective for identifying one or morecomponents of an intravenous fluid during administration of the fluid toa subject using one or more sensors. The one or more sensors arepreferably selected to include at least one sensor other than a flowsensor, and/or in some embodiments also preferably other than a pressuresensor, and/or in some embodiments also preferably other than anultrasonic sensor. Generally for example, preferred sensors effectivewith the apparatus, systems and methods of the invention can include,without limitation, one or more sensors selected from an impedancesensor (e.g., an AC impedance spectroscopy sensor), an electrochemicalsensor (e.g., an electrochemical potential sensor), a thermal sensor(e.g., a thermal anemometer sensor), an optical sensor (e.g., arefractometry sensor, a transmission sensor, an absorbance sensor, aspectrometer (including a colorimeter)r, a turbidity sensor), aTheological sensor (e.g., a viscometer), an electrical property sensor(e.g., a capacitor sensor, a pH sensor, a conductivity sensor, and aninductive sensor), and a fluid-displacing (e.g., resonator) sensor. Thevarious specific sensors and sensing approaches as described herein arepreferred, an can be generally used with any aspects, embodiments andapproaches described herein; however, many aspects, embodiments andapproaches of the invention do not require such certain specific sensorsor sensing techniques and can be effected independently thereof.

Generally, the sensor can be adapted for identifying an anticoagulant,preferably heparin. Preferably the sensor is adapted for determining oneor more properties of the fluid selected from electrochemical potential,impedance, refractive index and ultraviolet absorption, and foridentifying an anticoagulant, preferably heparin, based on the one ormore determined properties.

Generally, the sensor can be adapted for identifying ametabolically-active hormone, preferably insulin. Preferably, the sensoris adapted for determining one or more properties of the fluid selectedfrom electrochemical potential, impedance, refractive index and visibleabsorption (color), and for identifying a metabolically-active hormone,preferably insulin, based on the one or more determined properties.

Generally, the sensor can be adapted for identifying an anesthetic,preferably propofol. Preferably, the sensor is adapted for determiningone or more properties of the fluid selected from electrochemicalpotential, impedance, refractive index and visible absorption (color),and for identifying an anesthetic, preferably propofol, based on the oneor more determined properties.

Generally, the sensor can be adapted for identifying an analgesic,preferably morphine. In some variations, the sensor is adapted fordetermining one or more properties of the fluid selected fromelectrochemical potential, impedance, refractive index and ultravioletabsorption, and for identifying an analgesic, preferably morphine, basedon the one or more determined properties.

Generally, the sensor can be adapted for identifying one or morecomponents selected from the group consisting of a metal ion, a halideion, an organic ion or salt, and a sugar.

Generally, the sensor can be adapted for identifying potassium chloride,potassium ion or chloride ion. Preferably, the sensor is adapted fordetermining one or more properties of the fluid selected fromelectrochemical potential, impedance, refractive index and ultravioletabsorption, and for identifying potassium chloride, potassium ion orchloride ion based on the one or more determined properties.

Generally, in each of the above preferred embodiments, the sensor can beadapted for determining two or more properties of the fluid, and foridentifying the one or more active pharmaceutical agents based on thetwo or more determined properties.

Preferred sensors and fluid properties for sensing various activepharmaceutical agents (e.g. drug formulations) and other components areshown in Table 2.

TABLE 2 Preferred Fluid Properties and Sensors for Various FluidComponents Example Fluid Property Sensor Approach Reference Complexconductiv- AC impedance spectroscopy  (1) ity or admittance Ionicproperties Electrochemical potential  (2) Thermal properties Pulsedthermal anemometry,  (3) Index of refraction Refractometer, fiber optic (4) refractometer Optical absorption Optical absorption spectrometry (5) Color Spectrometer, colorimeter  (6) Viscosity Viscometer,resonator  (7) Density Viscometer, resonator  (8) Dielectric constantCapacitor, resonator  (9) Turbidity Turbidity sensor (10) PermeabilityChemical sensors with selective (11) membranes Ph Ph meter, MEMS Phsensor, chemical (12) color change sensor, litmus (e.g., paper)Conductivity DC and or AC conductance (13) Air bubbles Optical (14)Surface plasmon Surface Plasmon sensor (15) effects Thermal lensingOptical detection of refractive index (16) change Sono-luminescenceColorimetric and spectral detection of (17) spectroscopy species Flowrate Thermal anemometer, Doppler flow (18) meter

Generally, such sensor approaches and fluid-property measurements asshown in Table 2 can be effective for identification of one or moreactive pharmaceutical agents, or an intravenous solution component(e.g., saline, potassium chloride, dextrose, etc), in each case withinan intravenous fluid during administration of the fluid to a subject.Chemical sensors with selective membranes can differentiate fluidpermeability and be useful for example for identifying specificcompounds selectively (e.g., based on selection of a particularmembrane). Optical detection of air bubbles, can be effective forexample for preventing an air embolism, and additionally oralternatively, for detecting flow system failures (and thereby helpingto maintain flow). Measurement of flow rate by thermal anemometer and/orby Doppler flow meter can be effective, for example, for detectingblockages, controlling flow rate, determining dosing and detecting flowsystem failures (and thereby helping to maintain flow).

Without limitation, and without being bound by theory not expresslyrecited in the claims, the following references are representativeexamples of the sensor approach and/or the fluid property measurement asshown in Table 2:

-   (1) Impedance based flow sensors Green, N. G., Tao, S., Holmes, D.    and Morgan, H. (2005) Impedance based flow sensors. In:    Microtechnologies for the New Millennium 2005 SPIE, 9-11 May 2005.-   (2) http://www.resonancepub.com/electrochem.htm-   (3) A pulsed-wire technique for velocity and temperature    measurements in natural convection flows; Journal Experiments in    Fluids; Publisher: Springer Berlin/Heidelberg; ISSN 0723-4864    (Print) 1432-1114 (Online) Issue Volume 18, Numbers 1-2/December,    1994-   (4) Refractive Index Measurement and its Applications; Shyam Singh    2002 Phys. Scr. 65 167-180 doi: 10.1238/Physica.Regular.065a00167-   (5) http://www.doas-bremen.de/paper/spec_euro_(—)06_richter.pdf-   (6)    http://www.optek.com/Application_Note/General/English/7/Inline_Process_Color    Measurement.asp-   (7)    http://www.coleparmer.com/techinfo/techinfo.asp?htmlfile=why-meas-viscosity.htm&ID=933-   (8) Simultaneous Measurements at U-tube Density Sensors in    Fundamental and Harmonic Oscillation; Krasser, E.; Senn, H.;    EUROCON, 2007. The International Conference on “Computer as a Tool”;    Volume, Issue, 9-12 Sep. 2007 Page(s): 551-555-   (9) www.tmworld.com/contents/pdf/tmw03_(—)05 D1Jr.doc-   (10) http://www.omega.fr/techref/ph-6.html-   (11) A new method for the determination of membrane permeability by    spatially resolved concentration measurements; Bemd Schirmer et al    2004 Meas. Sci. Technol. 15 195-202 doi: 10.1088/0957-0233/15/1/027-   (12) http://www.sensorland.com/HowPage037.html-   (13) Sensor for measuring surface fluid conductivity in vivo;    Fouke, J. M.; Wolin, A. D.; Saunders, K. G.; Neuman, M. R.;    McFadden, E. R., Jr. Biomedical Engineering, IEEE Transactions    Volume 35, Issue 10, October 1988 Page(s): 877-881-   (14)    http://www.us.endress.com/eh/sc/America/us/en/home.nsf/imgref/D7A94F680B2EA516C12    573A8007833A6/$FILE/TI921 C-OUSAF13.pdf-   (15) Surface Plasmon Resonance Based Sensors; Springer Series on    Chemical Sensors and Biosensors, Vol. 4 Homola, Jiri (Ed.) 2006,    XII, 251 p. 134 illus. Hardcover ISBN: 978-3-540-33918-2-   (16) Flowing thermal lens micro-flow velocimeter; Yoshikuni    Kikutania, b, Kazuma Mawataria, b, Kenji Katayamaa, b, Manabu    Tokeshia, b, c, Takashi Fukuzawac, d, Mitsuo Kitaokab and Takehiko    Kitamor; Sensors and Actuators B; Chemical; Volume 133, Issue 1, 28    Jul. 2008, Pages 91-96-   (17) Malcolm J. Crocker, Handbook of Acoustics, Ch. 4, 1998-   (18) A thermoelectric sensor for fluid flow measurement, principles,    calibration and solution for self temperature compensation; H.    Stachowiaka, S. Lassuea, A. Dubernarda and E. Gaviotb; Flow    Measurement and Instrumentation; Volume 9, Issue 3, September 1998,    Pages 135-141.

Generally, and preferably, the apparatus, systems and methods of theinvention are directed to or effective for identifying one or morecomponents of an intravenous fluid during administration of the fluid toa subject using a sensor having a sensor element (e.g., with a sensingsurface adapted for interaction with and being responsive to theintravenous fluid), where such sensor element (e.g., such sensingsurface) is positioned at a location within an intravenous fluid systemsuch that it interacts with the fluid (e.g., such sensing surfacecontacts the fluid) in relative proximity to the infusion location—thelocation at which the fluid enters a subject's vasculature system.

In various embodiments of various aspects of the invention, therefore,the apparatus, systems and methods of the invention comprise a sensorelement (e.g., having a sensor surface) positioned proximal to (e.g., ator near) the distal end of a fluid line assembly, and/or proximal to aninfusion device. For example, with reference to FIGS. 1A through 1C andto FIG. 2, such a sensor 500 can comprise a sensor element 502 which caninclude a sensing surface 504 in a cavity 540 of an in-line housing 530,where the in-line housing optionally has inlet 510 and outlet 520, eachconfigured with fittings 212 (e.g., Luer Locks), and can be integratedinto the fluid line assembly upstream of an infusion device 300.Alternatively, for example, and with reference to FIGS. 3A through 3C,such a sensor element 502 can include a sensing surface 504 in a cavityof a housing (hub 330) defined in infusion device 300 (e.g., catheter,needle, etc.). Preferably, with further reference to FIGS. 3A through3C, the sensor element can be integrated into an intravenous infusiondevice such as a catheter. In exemplary embodiments, for example, theinfusion device can have a first end adapted for fluid communicationwith a fluid line assembly, a second distal end adapted for insertionthrough the skin into the vasculature system of the subject, preferablythrough a peripheral vein, and a housing (e.g., the hub of a catheter)providing excorporal structural support and having a cavity providingfluid communication between the first end and the second distal end ofthe intravenous infusion device. For example, such housing can beintegral with the hub of a catheter. One or more sensor elements caneach have a sensing surface positioned within the cavity for contactwith the fluid.

Optionally, in some embodiments, the apparatus, systems and methods ofthe invention can comprise one or more first sensor elements positionedproximal to the distal end of a fluid line assembly, and/or proximal toan infusion device, at least one injection port (including for examplefluid line from an intravenous pump subsystem) upstream of such firstsensor elements, and one or more additional second sensor elementspositioned upstream of such injection port—facilitating for example adifferential measurement approach. Significantly, such second sensorelement(s) can be configured to detect a baseline intravenous fluid(e.g., saline or Ringer's lactate), thereby providing a basis tocompensate measurements made with the first sensor element(s) for thebaseline signal, as well as for any background signal noises associatedwith the baseline fluid. Such a configuration can improve overall sensorsensitivity, and can thereby enable measurement and identification ofcomponents in more complex intravenous compositions. The second upstreamsensors can be positioned in the intravenous fluid source container orproximal thereto, for example in a fluid line proximal to an intravenousfluid source container.

Generally, the sensors of the invention can be used in combination withone or more additional sensors, including without limitation sensorssuch as thermal (e.g., temperature) sensors and/or flow sensors. Forexamples, a thermal (e.g., temperature) sensor can include a resistancetemperature detector (RTD) configured as known in the art. For example,flow sensors can include a set of two or more physically separatedsensor elements, which can determine flow based on detection of aspecific component at each sensor element over a measured period oftime. Other known approaches for flow sensor(s) can also be effected.For example, flow sensors based on Doppler flow measurement,thermo-annemometer measurement, electro anemometer measurement and/oracoustic anemometer measurement can be effected in combination withsensors of the invention.

Generally, the one or more sensor elements can be activated using anactivation circuit. The activation signal is not narrowly critical, andcan comprise for example a sinusoidal or non-sinusoidal (e.g., squarewave) activation signal (e.g., a voltage or current). In each case, theactivation signal provided to the sensor element(s) can have a varyingamplitude, a varying frequency and/or can be a pulsed signal. Non-steadyor modulated wave forms, such as amplitude modulated (AM) or frequencymodulated (FM) or pulse modulated (PM), or a combination of any of theforegoing can be employed. In some embodiments, the activation signalcan include an alternating current (AC) signal, and can optionallyfurther include a direct current (DC) bias signal. Such a DC bias signalcan be varied during measurement of a fluid property or condition. Insome embodiments, multiple frequencies can be applied and detected,serially or in some cases, simultaneously applied and detected. In someembodiments, one or more sensor elements can be activated with abroad-band “white noise” excitation signal having a wide range ofcontinuous frequencies. Such an approach allows for detection ofdifferences from such continuous frequencies. Otheractivation/excitation approaches are known in the art.

Generally, one or more sensor elements activated with an activationsignal in the presence of a intravenous fluid can generate a responsesignal which is dependent upon or influenced by the composition of suchintravenous fluid. The response signal can be conditioned (e.g.,amplified, biased, etc.) for example in a (local or remote) signalconditioning processor (e.g., comprising one or more signal processingcircuits), and can be optionally transmitted to a (remote or local)signal identification processor. Calibration signals can be developedand provided corresponding to known pharmaceuticals or other fluidcomponents, or to a baseline intravenous fluid (e.g., saline or Ringers'lactate) to aid in identification of a component of an intravenousfluid. One or more identifier circuits can be effected to correlate ameasured signal to a specific patient or a specific device. One or moremonitoring circuits can be effected to provide for communication to ahuman through a user interface, and/or for comparative monitoring (e.g.,against a selected setpoint). Other circuits and processors can be used,as described in further detail throughout this specification and/or asotherwise known in the art.

Multi-Parametric Approaches

Generally, and preferably, the apparatus, systems and methods of theinvention are directed to or effective for identifying one or morecomponents of an intravenous fluid during administration of the fluid toa subject using a multi-parametric approach. In such approach, multipleparameters (e.g., multiple fluid properties such as without limitationrefractive index, electrochemical potential, impedance, admittance,conductivity, etc.) can be sensed, and the combination of parameters canbe correlated to obtain resolution of components within the fluid.Hence, an intravenous fluid can be sensed—for example with multiplesensors (or with a sensor having multiple sensor elements) and/or withmultiplexing of a sensor element to obtain independent sensingmeasurements—to generate a multi-parametric profile characteristic ofcomponent identity within the fluid. A multi-parametric profile can becorrelated to determine an identity of one or more components of thefluid. Such multi-parametric approaches advantageously provide forimproved resolution of components; therefore such approaches allow forimproved ability to distinguish between different fluid compositions,including for example the presence or absence of particular activepharmaceuticals, and/or various concentrations of a particular activepharmaceutical or other component.

With further reference to FIG. 4, for example, a sensor can comprise twoor more sensor elements 502, each having a surface positioned within acavity (e.g., 540, 340) of a housing (e.g., 530, 330) for contact withthe fluid. The housing can be adapted for fluidic interface with a fluidline assembly of a system for intravenous delivery of fluid into apatient, or can be defined in an intravenous infusion device. As shownin FIG. 4, each of the sensor elements can be passively monitored,and/or can be activated using an activating circuit, and the response ofeach of the sensor elements can be acquired and processed in a processorcircuit. The various responses can be correlated to identify acharacteristic profile of the one or more components in the fluid. Seefor example, Examples 2, 3 and 4.

Generally therefore, and with further reference to FIG. 4, in preferredembodiments the apparatus, systems and methods of the invention compriseor use at least two or more sensors or an integrated assembly comprisingtwo or more sensors (e.g., an integrated assembly comprising two or moresensor elements, each sensor element comprising one or more sensingsurfaces). Preferably, such two or more sensors are of different typesand/or having different sensor approaches (e.g., impedance sensor,thermal sensor, electrical property sensor, optical sensor, etc.)thereby enabling for orthogonal fluid property measurements. As anon-limiting example, such two or more sensors can include two or moreof an impedance sensor (e.g., an AC impedance spectroscopy sensor), athermal sensor, and/or an optical sensor (e.g., a refractometry sensor,a transmission sensor, an absorbance sensor, a spectrometer (including acolorimeter) or, a turbidity sensor). Preferably, such two or moresensors can be integrated into a common assembly, such as a commonsubstrate, e.g., as part of a common sensor subunit, as discussed belowin connection with FIG. 6C through FIG. 6G. As a non-limiting example,two or more of an impedance (e.g., AC impedance) sensor, a thermal(e.g., a resistance thermal detector) sensor, and an optical (e.g.,refractive index) sensor can be employed in combination.

In a preferred embodiment, at least one sensor is an electricalproperties sensor such as an impedance sensor. Independent electricalproperty (e.g., impedance) measurements can be derived, for example,from a set of two or more sensor elements having sensing surfacesdefined by electrodes consisting essentially of different metalmaterials. Preferred metals include noble metals and other chemicallyinert transition metals, such as without limitation, Au, Pt, Pd, Ag, W,Ti, Ni, Sn, Co and others. Electrical property measurements such asimpedance measurements can preferably be effected using different paircombinations of three or more sensor elements. For example, for a sensorcomprising sensor elements A, B and C, three pairs of sensor elementscan be used: an A-B pair, an A-C pair, and a B-C pair, with each of suchpairs defining an independent impedance measurement channel. As anotherexample, for a sensor comprising five sensor elements A, B, C, D and E,such five sensor elements can be paired to define ten independentimpedance measurement channels: A-B, A-C, A-D, A-E, B-C, B-D, B-E, C-D,C-E, and D-E. Such impedance sensor elements can be activated usingalternating current (AC), allowing for determination of both real andimaginary (complex) impedance response for each pair of sensor elements.Hence, three sensor elements can provide for six independent measurementchannels at each applied AC frequency for determining the identity of acomponent of the intravenous fluid. Generally, the number of discreteindependent impedance sensor elements can range from 2 to 100, from 2 to50, from 2 to 20 or from 2 to 10. Pairs of sensor elements can beactivated using multiple (different) frequencies. If five frequenciesare used for activating an impedance sensor comprising three sensorelements, for example, then the impedance sensor effectively providesfor thirty independent measurement channels for determining the identityof a component of the intravenous fluid (three sensor elements->threechannels×real and imaginary components->two channels=six channels perfrequency×five frequencies->thirty channels). Generally, the number ofdiscrete independent frequencies can range from 1 to 100, preferablyfrom 2 to 100, from 2 to 50, from 2 to 20, from 2 to 10 or from 2 tofive or from 2 to 3. Similarly, pairs of sensor elements can beactivated at multiple (different) amplitudes, with a similar multipliereffect on multi-modal measurements. Generally, the number of discreteindependent amplitudes can range from 1 to 100, preferably from 2 to100, from 2 to 50, from 2 to 20, from 2 to 10 or from 2 to five or from2 to 3. Further variations, such as use of different inputsignals—sinusoidal, step-wave, pulse, etc.—can provided for additionalindependent channels in a multiparametric context.

Analogous multiplexing can be effected with other sensors types (e.g.,optical, electrochemical potential, etc.).

Processing of the signal acquired from each of a plurality of sensorscan be effected in a signal identification processor. Such processor cancomprise signal conditioning circuits for conditioning one or moresignals (e.g., for amplifying, biasing) prior to or during furtherprocessing. Such processor can employ software or firmware or caninclude an application specific integrated circuit (ASIC) effective forand/or adapted to recognize and distinguish between signals correlatingto components of an intravenous fluid. Such software can comprisepattern recognition algorithms known in the art. In one relativelysimple algorithm, for example, sensor signals can be processed torecognize the identity of component substances by measuring produceddeviations—e.g., in various directions by supplying the values for theexpected angles. See for example, Example 4. See also for example, J.Ross Macdonald, Impedance Spectroscopy Theory, Experiment, andApplications (2005).

For example, in embodiments where a set of two or more sensor elementshaving sensing surfaces defined by metal electrodes are exposed to afluid, and activated by energizing with an AC voltage or current, theresulting complex current or voltage can be measured. When theactivating signal is sufficiently small, the system can respondlinearly, and may be modeled in terms of complex AC impedance oradmittance, e.g. having real (x) and imaginary (y) response components.The measured values of x and y as well as their relative magnitudechange predominantly with the electrical properties of the fluid flowand fluid-electrode interface, both of which are heavily affected by thecomposition of the flow. The change in these values can be correlated tothe nature of the fluid material and can be used to identify theparticular component of the intravenous fluid. As demonstrated inExample 4, for example, highly diluted components injected into salineflow can be identified by such sensors. Generally, a deviation distancefrom a data point corresponding to pure saline or Ringer's lactatedepends on both concentration and molecular or ionic composition of thecomponent, while deviation direction from such data point dependspredominantly on the molecular or ionic composition of the component.For higher concentrations of the component, both magnitude and directionof the deviation become concentration-dependent in unique anddistinguishable manner which is specific to and dependent upon theparticular component added to the saline. Hence, such deviationdependencies enable identification of components having differentcompositions or concentrations. For example, pattern recognitionalgorithms can be adapted to recognize substances that are components ofan intravenous fluid. A data signal from sensors can result indeviations from baseline data corresponding to the backgroundcomposition of the intravenous fluid (e.g., saline or Ringer's lactate),including deviations in magnitudes and/or deviations in directions, theangles for each of which can be determined as described above andexemplified in Example 4. In subsequent operation, such software cancompare measured angles determined from detected data with the valuesfor expected angles corresponding to certain substances, therebyidentifying the substances. Such pattern recognition algorithms can beadvantageously applied to the differentiation and recognition of datagenerated by the sensors in multi-dimensional space. Additionally,software can be used to determine the cumulative dosing of a componentof a fluid, as well as a projected dosing over a certain upcoming periodof time. For example and without limitation, once a component isidentified, a current cumulative dosing level can be measured byintegrating the signal corresponding to that component over time duringthe period defined from when the signal exceeded a detection thresholdto the current time (e.g., taking into account the sensor sensitivity toidentified substance and the volumetric flow). Projected dosing levelscan extrapolate the component composition and extend the time period fora defined period.

Adaptations on such algorithms are known in the art. Moreover, moreelaborate pattern recognition algorithms can be applied to thedifferentiation and recognition of curves generated by themultiparametric sensor system in multi-dimensional space. See, forexample, Sing-Tze Bow, Pattern Recognition and Image Preprocessing(2002); M. S. Nixon, A. S. Aguado, Feature Extraction and ImageProcessing (2002); and D. Maltoni, D. Maio, A. K. Jain, S. Prabhakar,Handbook of Fingerprint Recognition, 2002. Examples of other patternrecognition software include without limitation artificial neuralnetwork and fuzzy logic algorithms.

Preferred Circuit Configurations/Monitoring Approaches

Generally, and preferably, the apparatus, systems and methods of theinvention are directed to or effective for identifying one or morecomponents of an intravenous fluid during administration of the fluid toa subject (e.g., a specific patient, for example at a hospital, clinic,surgical environment, home hospice, nursing home, assisted livingenvironment, etc), where such subject is positively and specificallyidentified in connection with monitoring and administration of theintravenous fluid. Various embodiments and aspects of the invention caninclude approaches for correlating the sensor data (i.e., data (e.g., asrepresented by a signal) originating from the sensor—either raw data ormore typically processed data) to a specific subject (e.g., patient).For example, the sensor (or apparatus or system comprising a sensor) caninclude an identifier circuit for correlating sensor data to a specificsubject. Typically, and preferably, such identifier circuit may be incommunication with one or more other circuits, including for examplecircuits for receiving processing, storing, displaying or transmittingdata, including data originating from the sensor element, such as asignal processing circuit or a data retrieval circuit. Such integratedpatient-identification approaches can further enhance the benefit topatient safety, by reducing the potential for errors associated withintravenous administration, and especially intravenous drugadministration.

Generally, and preferably, the apparatus, systems and methods of theinvention are directed to or effective for identifying one or morecomponents of an intravenous fluid during administration of the fluid toa subject with a remote and/or centralized monitoring approach. Althoughsuch remote and/or centralized monitoring approaches can be effected foran individual subject (e.g., in a home hospice environment), suchapproaches are especially advantageous in connection with multi-subjectcare environments. For example, different sensor data from one subjector from several different subjects (in each case, such sensor data beinglocally generated and specifically associated with an intravenous fluidbeing administered to a particular subject) can be acquired and/ormonitored at a location which is remote (relative to the patient)—suchas a nursing station; preferably such sensor data can be centrallymonitored at such remote location. In various aspects and embodimentstherefore, and with reference to FIGS. 1B and 1C, FIG. 2, and FIGS. 3Athrough 3C, for example sensor data, can be generated in a processor 550local to and in communication with a sensor element 502 (e.g., having asensing surface in contact with the intravenous fluid), preferably foreach of two or more subjects, and then such locally-generated sensordata stream(s) can be acquired by a processor 600 remote from the sensorelement 502. Such acquisition can be effected, for example, via wireless(e.g., Bluetooth®) or other communication approaches. The localprocessor 550 can be in communication with the sensor element 502, andparticularly with a sensing surface 504 thereof, for example through oneor more releasable contacts 508 and one or more electrical connections506. The local processor 550 can be permanently integrated orintermittently integrated (temporally limited engagement) with thesensing element 502 as described below.

The remote processor 600 can comprise one or more circuits forreceiving, processing, storing, displaying or transmitting the acquiredsensor data. The acquired sensor data can be monitored remotely,including for example at a central monitoring location. Preferably forexample, the monitoring can be done visually by human interaction with adisplay and/or can be further enhanced and effected by various automatedapproaches. In one such automated monitoring approach, a monitoringcircuit can comprise a data comparator module for comparing one or moreparameters (e.g., data values) derived from sensor data with one or moreparameters (e.g., data values) which are prescribed or proscribed for aparticular subject (e.g. patient). Such patient-relevant parameters canbe treatment-centric (e.g., applicable to all such patients undergoing aparticular treatment), including semi-customized treatment-centricparameters which include a patient-specific data input (e.g., a patientweight, patient age, etc.) to determine a treatment-centric parameter,and/or such patient-relevant parameters can be patient-centric (e.g.,wholly customized for a specific patient). Exemplary non-limitingparameters can include dosing levels, dosing timing (onset orcompletion), dosing frequency, etc. for various and specific activepharmaceutical agents or other components of an intravenous fluid.Patient-relevant parameters can be specific for the intravenousmonitoring system effected by the apparatus, systems and methods of theinvention, and/or can be common with (e.g., shared with) various othersystems, such as infusion pump systems (e.g., “smart pumps”).Advantageously, the monitoring approaches of the apparatus, systems andmethods of the invention can also include certain notice (e.g., alarm)features—to provide notice to a caregiver that a specific patient'sintravenous fluid delivery system is operating incongruous with aprescribed or proscribed treatment, and/or can also include certaincorrective action (e.g., system control) features—to make, preferablyautomated, a corrective action with the intravenous fluid deliverysystem. For example, upon determining an inconsistency betweencorresponding sensor-data-derived parameter and prescribed or proscribedpatient-relevant parameter, an alarm can sound and/or a control circuitcan activate a control element (e.g., an automated infusion valve) tomake a change in the intravenous administration regime. Such remoteand/or central monitoring approaches can further enhance the benefit topatient safety, by reducing the potential for errors associated withintravenous administration, and especially intravenous drugadministration.

Generally, and preferably, the apparatus, systems and methods of theinvention are directed to or effective for identifying one or morecomponents of an intravenous fluid during administration of the fluid toa subject with a sensor that comprises a processor (e.g., as includedwithin a processor assembly) which is physically separable from, andintermittently interfaceable with (e.g., for a finite, operationallyeffective period of time) a sensor element (e.g., as included within ahousing assembly). The approach of a temporally-limited engagement(interfacement) of the processor and the sensor element allows forregular operation while engaged/interfaced, and allows for physicalseparation of sensing function and processing function of a sensor (atleast for some period of time) after or between operations, with acorresponding separation of physical treatment of the embodiments whicheffect such function. For example, and with reference to FIG. 1B, FIG.2, and FIGS. 3A through 3C, the sensor element 502 can be physicallyseparated from the processor 550 for a period of time to allow forsterilizing the sensor element 502 (or a sensing surface 504 thereof) orfor disposal and replacement of a (pre-) sterilized sensor element 502(or a sensing surface 504 thereof). Such separation also allows forre-use of the processor 550—for example, in connection with a secondsubsequent subject. The processor 550 can be engaged for example througha processor guide 552. Significantly, since processors 550 are generallymore expensive than sensor elements 502 (or sensing surfaces 504thereof), the re-use of processors 550 in such a temporally-limitedengagement (interfacing) approach provides for efficiency of capitalinvestment, especially in a multi-subject (e.g., hospital, surgical,nursing care, etc.) environment.

In any of the aforementioned approaches and in any of the aspects andembodiments of the invention, the monitoring system can include alogging circuit for recording (e.g., storing) sensor data over time. Thelogging circuit can be in accessible communication with a displaycircuit for intermittent (temporally-limited) display of sensor data orof a patient-relevant parameter derived from sensor data. In operation,for example, the logging circuit can record sensor data withoutdisplaying such data (or a patient-relevant parameter derived therefrom)unless and until specifically requested (e.g., by a caregiver based onthat caregiver's discretion, and/or by another circuit, such as by thecomparator module of the monitoring circuit when there is an incongruitybetween a sensor data parameter and a prescribed or proscribedpatient-relevant parameter) to be displayed. Display, such as automateddisplay during an abnormal operational event can help a caregiverunderstand a situation more quickly and thereby reduce the risk of acompounded error and improve the corrective treatment regime.Additionally or alternatively, such display can be effected ex-postfacto to reconstruct facts regarding the patient experience based onlogged sensor data.

Various preferred schema for circuit configuration and operation areshown in FIGS. 5A and 5B. With reference to FIG. 5B illustrated is ahigh-level schematic diagram showing various circuits and onearrangement for their interrelationship with local processor and remoteprocessor, and/or with housing assembly and processor assembly. FIG. 5Aillustrates a block diagram of a specific preferred circuitconfiguration for a reader unit comprising a microcontroller. Thecircuits of such reader unit can include, for example, one or more ofany of an activation circuit, a data retrieval circuit, a signalprocessing circuit, an identifier circuit, a data acquisition circuit,and/or a monitoring circuit. Preferably, one or more of any suchcircuits can be adapted into a signal conditioning processor and/or asignal identification processor. Such circuits can be included, forexample, in a processor assembly for intermittentlyinterfacing/temporally-limited engagement with a sensor element.Alternatively, some of such circuits could be in a housing assembly—seefor example FIG. 5B. Preferably, with reference again to FIG. 5A, thereader unit can be programmed when a patient is admitted for treatment.The reader unit can receive and store the identification informationabout the patient either through RF interface or through I/O interfacefrom the admitting database information, for example in an identifiercircuit. The reader unit can be physically co-located adjacent to orattached to the patients, for example as a bracelet, or adhesivelyattached to a patient's skin. Once the identification information isreceived, and the processor assembly is interfaced with a housingassembly (described herein), the reader unit can commence broadcastingidentifier information, for example wirelessly via RF interface such asWiFi or Bluetooth® interface, continuously or periodically.Alternatively the unit can be connected via direct connection (e.g.,electrical wire or optical cable) to a bedside monitoring system, whichcan itself send patient identification information through I/Ointerface. Along with patient identification information the unit canalso send information regarding the status of the interface between theprocessor assembly and the housing assembly (e.g., whether engaged(operable) or disengaged (non-operable). Once a patient has received anintravenous line, and when the unit is engaged for operation, throughthe interface to the sensing unit—the reader can verify the connection,energize or activate the sensors, and sense and transmit data from thesensor element, and preferably from a local processor to a remoteprocessor included within a monitoring unit, for example via anysuitable communication approach such as hospital radio frequency port;alternatively the monitoring can be local, such as via bedsidemonitoring equipment.

Additional preferred schema for an integrated sensor and circuitconfiguration are shown in FIGS. 5C through 5E. Generally, suchconfiguration can include a sensor that comprises (i) an assemblycomprising one or more sensor elements 502, (ii) a signal-conditioningprocessor (e.g., optionally included within a local processor 550 (whichcan, optionally, be physically separable from and/or be intermittentlyinterfaceable with the sensor element 502) or included within a remoteprocessor 600), and (iii) a signal-identification processor, includingone or more circuits adapted for identifying or determining a signalrepresentative of the identity of one or more components of anintravenous fluid (e.g., optionally included within a local processor550 (which can, optionally, be physically separable from and/or beintermittently interfaceable with the sensor element 502) or includedwithin a remote processor 600). With reference to FIG. 5C for example,in one such preferred subembodiment, each of the assembly comprising theone or more sensor elements 502, the signal-conditioning processor (550or 600), and the signal-identification processor (550 or 600) are eachphysically separate components. In an alternative of such preferredsubembodiment, represented schematically in FIG. 5D, the assemblycomprising the one or more sensor elements 502 is physically separatefrom an integrated assembly comprising the signal-conditioning processor(550 or 600) and the signal-identification processor (550 or 600). Inanother subembodiment shown in FIG. 5E, each of the one or more sensorelements 502, the signal-conditioning processor (550 or 600), and thesignal-identification processor (550 or 600) are integrated into acommon (integrated) assembly. Such various approaches for configuringthe sensor elements, the signal-conditioning processor and thesignal-identification processor are preferred, an can be generally usedwith any aspects, embodiments and approaches described herein.

FIG. 6 (A, B) illustrate schematic representations of various sensors,including an optic fiber refractive index sensor (FIG. 6A) and anelectrical property sensor (e.g., which can be configured and employed,for example, as an impedance sensor or for example, as anelectrochemical potential sensor) (FIG. 6B). Such sensors and othersdescribed herein are known in the art. Briefly, with reference to FIG.6A, an optical sensor can comprise a fiber optic, such as a flexiblefiber optic formed in a U-shape, and having an optical entrance 501, asensor element 502 defined by the curved region of fiber optic exposedto the intravenous fluid, and an optical exit 503 into a detector. Inoperation, a light can be admitted to the fiber optic, guided to thesensor element 502 and exposed to an intravenous fluid in communicationwith the sensor element 502. Variations in intensity of the lightcoupled from the entrance to exit are proportional to the refractiveindex of the fluid. The index of refraction can be fluid-compositionvariable, thereby providing a parameter for determining the identity ofthe fluid composition. See, for example, Examples 1, 2 and 3. Referringfurther to FIG. 6B, an electrical property sensor (e.g., impedancesensor, electrochemical potential sensor, etc.) can comprise a pluralityof sensor elements 502 a, 502 b, 502 c. For example, each of the sensorelements can comprise a sensing surface consisting of a material such asa metal, with the sensing surface of each such sensor element being thesame material, or in some embodiments a different material, such as adifferent metal. Preferably, metal materials are chemically inert withinthe fluid environment. Preferred metals include noble metals and otherchemically inert transition metals, such as without limitation, Au, Pt,Pd, Ag, W, Ti, Ni, Sn, Co and others. Each of the sensor elements 502 a,502 b, 502 c are in electrical communication with dedicatedcorresponding contacts 508 a, 508 b, 508 c, respectively, for example,through dedicated corresponding electrical connectors 506 a, 506 b, 506c. The sensor elements 502, contacts 508 and electrical connectors 506can be formed or supported on a common substrate, such as commonmicrofabrication substrate. In operation, the electrical property (e.g.,impedance or electrochemical potential) associated with each of thesensor elements 502 a, 502 b, 502 c can be measured independently andsimultaneously, proving for three independent real-time channels formultiparametric characterization of a component within an intravenousfluid.

A preferred sensor embodiment can comprise an integrated assemblycomprising two or more sensor elements, such as impedance sensorelements, thermal sensor elements and/or refractive index sensorelements. With reference to FIG. 6C through FIG. 6G, for example, anintegrated sensor assembly can comprise one or more substrates, such asa first sensor element substrate 520 and comprising two or more sensorelements. The first sensor element substrate 520 can have a first (topas shown) surface 521 and a second (bottom as shown) surface 522. Asdepicted, and with specific reference to FIG. 6C, FIG. 6D and FIG. 6E(showing detail of tip portion of the sensor element substrate of FIG.6D) for example, the first substrate can comprise impedance sensorelements 502 b, 502 c, 502 d, and also thermal sensor elements 502 a,502 e. The impedance sensor elements 502 b, 502 c, 502 d, and thethermal sensor elements 502 a, 502 e, can each comprise a sensingsurface defined by a metal electrode. The metal electrode preferablyconsists essentially of a chemically inert, conductive material. Metalsor metal compositions comprising noble metals and other transitionmetals are preferred. Examples include Au, Pt, Pd, Ag, W, Ti, Ni, Sn, Coand others. Preferably, the impedance sensor elements 502 b, 502 c, 502d each comprise a sensing surface defined by different types of metals(e.g., where 502 b, 502 c, 502 d have a sensing surface defined byelectrodes consisting essentially of Au, Pt, Pd, respectively). Thethermal sensor elements 502 a, 502 e can each comprise a sensing surfacedefined by the same type of metal (e.g., Au). Electrical connectors 506b, 506 c, 506 d provide a conductive path (for signal communication)between impedance sensor elements 502 b, 502 c, 502 d and correspondingcontacts 508 b, 508 c, 508 d, respectively. Similarly, electricalconnectors 506 a, 506 e, provide a conductive path (for signalcommunication) between thermal sensor elements 502 a, 502 e, andcorresponding contacts 508 a, 508 e, respectively. As depicted, and withspecific reference to FIG. 6C, the first substrate 520 can also comprisea refractive index sensor element 502′ integrally configured within thebody of the first substrate 520. As shown for example, such refractiveindex sensor element can comprise an optically transparent region of thesubstrate 520 defining a wave guide 524, 525, 526, and further definedby a region 528 of the substrate which is optically less transparent orsubstantially non-transparent. With specific reference to FIGS. 6F and6G, the integrated sensor assembly can further comprise a second cappingsubstrate 530 having a first (top as shown) surface 531 and a second(bottom as shown) surface 532. The second capping substrate 530 can beadapted with an aperture situated over and providing for fluid access tosensor elements 502 a, 502 b, 502 c, 502 d, 502 e, and being furtheradapted with apertures situated over and providing electrical access toeach of the contacts 508 a, 508 b, 508 c, 508 d, 508 e. In theconfigured sensor assembly, the first (top) surface 521 of the firstsensor element substrate 520 can be capped/sealed by integral contactwith the second (bottom) surface 532 of the second capping substrate530. Fabrication of such integrated subassembly can be facilitated byalignment pads 535 on the first surface 521 of the first substrate 520and spatially corresponding apertures in the second capping substrate530. As shown in FIG. 6F and FIG. 6G, the integrated sensor assembly canfurther comprise a functional communication port 536, such as a USBport, providing independent electrical communication with each of thecontacts 508 a, 508 b, 508 c, 508 d, 508 e.

In operation, with reference to FIGS. 6C and 6G, an intravenous fluidbeing measured can be in fluid communication with the curved tip portionof the integrated sensor assembly. The impedance sensor elements 502 b,502 c, 502 d can be activated using an activation circuit in electricalcommunication with these sensor elements through communication port 536,contacts 508 b, 508 c, 508 d and electrical connectors 506 b, 506 c, 506d, respectively. A responsive signal can be received from each of thesesensor elements by a data retrieval circuit in electrical communicationtherewith through the same independent communication paths. Threeindependent channels can be configured for impedance measurements—usingdifferent pairs of impedance sensor elements in combination—namely: (i)506 b-506 c; (ii) 506 c-506 d; and (iii) 506 b-506 d. Each of such pairsof sensor elements can be activated using alternating current (AC),allowing for determination of both real and imaginary (complex)impedance response for each pair of sensor elements. In thisconfiguration therefore, the impedance sensor can effectively providefor six independent measurement channels at each applied AC frequencyfor determining the identity of a component of the intravenous fluid.These pairs of sensor elements can be activated using multiplefrequencies. If five frequencies are used for impedance sensor elementactivation, for example, then the impedance sensor effectively providesfor thirty independent measurement channels for determining the identityof a component of the intravenous fluid. The thermal sensor elements 502a, 502 e can be variously configured, for example for measuringtemperature and or flow (e.g., as a thermal flow anemometer). In oneembodiment for example, thermal sensor elements 502 a, 502 e areconfigured as a resistance temperature detector (RTD), and can beactivated using an activation circuit in electrical communication withthese sensor elements through communication port 536, contacts 508 a,508 e and electrical connectors 506 a, 506 e, respectively. A responsivesignal can be received from each of these sensor elements by a dataretrieval circuit in electrical communication therewith through the sameindependent communication paths. The refractive index sensor can be usedsimultaneously and in combination with the impedance sensor elements 502b, 502 c, 502 d, and the thermal sensor elements 502 a, 502 e. Withreference to FIG. 6C, for example, incident light (e.g., from aninfrared light emitting diode (LED) source) can be admitted through aninlet end into a first section 524 of the wave guide, and allowed tointeract with the intravenous fluid in a second section 525 of the waveguide which defines the refractive index sensor element 502′. Theefficiency of light coupled through the waveguide is affected byrefractive index of a fluid into which the waveguide is immersed; theresulting signal is proportional to the fluid refractive index. Lightcan be retrieved through a third section 526 of the wave guide at anoutlet end of the wave guide into a photo-sensitive detector (forexample into an infrared phototransistor) configured for detecting theoutput light. A multimeter (e.g., a Keithley Model 2100 Multimeter) canmeasure voltage output of the photo-sensitive detector, and such outputsignal can be communicated to a data retrieval circuit. Generally, eachof the signals received from the impedance sensor elements, thermalsensor elements, or refractive index sensor element can be independentlyconditioned (e.g., amplified, biased, etc.) in signal processing circuitwithin a (e.g., local or remote) signal conditioning processor, and canprocessed in a signal identification processor (e.g., local or remote),for example using multiparametric analysis, to identify a component ofthe intravenous fluid. The identified component can be correlated to aspecific patient through use of an identifier circuit, as describedabove.

EXAMPLES Example 1 General Methods for Identifying Components Typical ofan Intravenous Fluid

In this example, materials were obtained from Sigma Aldrich anddissolved or diluted with 0.9% saline to reach the desiredconcentrations. Solutions of insulin, heparin and potassium chloridewere prepared at concentrations comparable to typical bolus doses usedin medical settings. All experiments were carried out using preparedsolutions contained in 20 ml glass vials. Samples were measured bydipping admittance and optical sensor probes into each vial such thatthe active area of each probe was fully submerged in the solution to betested. The response of each sensor to air and tap water were alsomeasured.

The admittance signal is measured using a probe constructed with noblemetal pads embedded in a polymer substrate. All measurements wereperformed at a frequency of 100 kHz. An Agilent Model 4395A networkanalyzer was utilized for measuring the admittance probe.

The optical sensor is constructed from a section of optic fiber with aninfrared LED fed into one end and an infrared phototransistor detectingthe output at the opposite end. The fiber jacket is removed along asection of its length and this section is bent into a curve. In thisconfiguration, the efficiency of light coupled through the fiber isaffected by refractive index of a fluid into which it is immersed andthe resulting signal is inversely proportional to the fluid refractiveindex. A Keithley Model 2100 Multimeter was used to measure the voltageoutput of the optical sensor phototransistor detector and all data isrecorded using a PC.

Example 2 Identification of Various Active Pharmaceutical Agents andOther Components Typical in an Intravenous Fluid

The sensor configuration and method described in Example 1 was used toidentify components typically included in intravenous fluids, includingpharmaceutical agents and other components. Specifically, the methodswere applied to identify potassium chloride (KCl), sodium chloride(saline) (NaCl), heparin, water, insulin and air using admittance andrefractive index sensors.

The results are summarized in Table 3, and shown graphically in FIGS.7(A-C) for measurements of admittance, real portion (FIG. 7A),admittance, imaginary portion (FIG. 7B), optical refractive index (FIG.7C).

A multi-parametric representation of such measurements is shown in FIG.7D. As observed from these results, the multi-parametric analysis anddata provide improved resolution of the various components of theintravenous fluid, and therefore allow for a more robust approach fordistinguishable measurement thereof. The multi-parametric profile can becharacteristic of the fluid component.

TABLE 3 Sensor Responses for Various Components Material AdmittanceAdmittance* Optical Signal KCL 64.310 55.094 2.084 Saline 25.368 12.8002.168 Heparin 14.200 3.775 2.144 Water 0.481 0.129 2.171 Insulin 5.8571.339 2.166 Air 0.010 0.141 2.210 Note 1: The optical signal isinversely proportional to refractive index. Note 2: Admittance denotesthe real admittance. Note 3: Admittance* denotes the imaginary (complex)admittance.

Example 3 Identification of Component Typical of Intravenous Fluid inDilution Series

A set of dilution series experiments were conducted, in whichconcentrated samples of heparain, insulin and potassium chloride wereeach diluted by half concentration a total of three times to giveconcentrations of 1, V£, %, and ⅛ of a typical bolus dose and each onemeasured using the admittance and optical sensors described in Example 1according to the approach described in Example 1.

The data for each dilution series of heparin, insulin and potassiumchloride are shown in Tables 4A, 4B and 4C, respectively. Concentrationis relative dilution. Admitt.=Admittance (real portion).Admitt.*=Admittance (imaginary portion).

These results are also shown graphically in FIGS. 8(A-C) formeasurements of admittance, real portion (FIG. 8A), admittance,imaginary portion (FIG. 8B), optical refractive index (FIG. 8C). Amulti-parametric representation of such measurements is shown in FIG.8D; the multi-parametric analysis and data demonstrate resolution ofthese various components at different concentrations.

Example 4 Identification of Intravenous Fluid Components withMulti-Channel Impedance Sensor

A set of experiments were conducted using a multi-channel impedancesensor comprising two sensor elements. The two sensor elements eachcomprised a sensing surface defined by circular gold electrodes, 0.32 mmdiameter, situated coplanar and at a distance of 0.75 mm from each otheron a wall of a non-conductive flow path. An intravenous fluid consistingof 0.9% saline was provided in an infusion bag set on hanger. A fluidline assembly comprising an intravenous dripper was inserted, and flowfrom the infusion bag was initiated at a typical infusion rate (−120cc/hr). The fluid line assembly comprised an injection port. Theaforementioned gold electrode sensor elements were provided downstreamfrom the injection port.

In this example, the sensor was used to measure the real and imaginaryimpedance of saline (0.90) flowing through the fluid line assembly atsteady state. A bolus (1 ml) of saline-diluted potassium chloride (10mg/ml) was injected into the flowing saline, and detected by the sensor.Independently and subsequently, a bolus (1 ml) of saline-dilutedmagnesium sulfate (40 mg/ml) was injected into the flowing saline anddetected by the sensor. Independently and subsequently, a bolus ofapproximately 1 ml of plain deionized water was injected into theflowing saline, and detected by the sensor.

In each case, both in-phase and out-of-phase components of the currentthrough the sensor were continuously recorded and plotted by the system.The real, in-phase component of the current was plotted along the X-axisand the imaginary, out-of-phase of the current was plotted along theY-axis of the chart. Briefly, a 100 KHz AC voltage of 8 mV amplitude wasapplied across the electrodes in series with a 50 Ohm resistor, and thevoltage drop across the resistor was measured using a Stanford ResearchModel SR830 lock-in amplifier. A microprocessor (a personal computer)was connected to the lock-in amplifier via RS232 interface with softwarerecording the complex voltage read by the lock-in amplifier at a datasampling rate of approximately twice per second. The data was plottedwith the real part of the measured voltage value along X-axis and theimaginary part—along Y-axis. In our experiments, an average x₀+iy₀ andstandard deviation σ were determined, accounting for naturally occurringnoise. A measured voltage value x+iy deviating from the average value by|Δx+iΔy|>6σ in any direction on the XY chart is a statisticallysignificant indication of a change in the fluid. In this case,arg(Δx+iΔy) defines the angular direction of the deviation vector. Twodeviations Δx₁+iΔy₁, and Δx₂+iΔy₂ are statistically distinguishable if|Δx₁+/Δy₁|>6σ and |Δx₂+iΔy₂|>6σ and |Δx₁−Δx₂+i(Δy₁−Δy₂)|>6σ. The latterinequality defines the relationship between the magnitude of thedeviations and the angle between them for the deviations to bedistinguishable from each other.

The values determined from the sensor in flowing saline resulted insubstantially overlapping data points, as shown on the plot included asFIG. 9A.

The bolus of saline-diluted potassium chloride (KCl) injected into thesaline flow through the injection port was detected by the sensor,resulting in a 2-dimensional characteristic signature for the KClcomponent. (See FIG. 9A). Multiple injections of potassium chloride(KCl) resulted in distinct substantially overlapping curves, as shown.Without being bound by theory not expressly recited in the claims,following injection of the saline-diluted potassium chloride into theflow as a bolus dose, the leading “front” edge of the flow profile forthe bolus reaches the vicinity of the electrodes, and the complexcurrent deviates from its average value in pure saline and returns backwhen trailing “back” edge of the flow profile for the bolus passes thevicinity of the electrodes, thereby producing the characteristicsignature. One can observe that the leading edge of the potassiumchloride injection produces deviation from the data point representingthe saline and that such deviation is nearly linear and at a distancefar greater than the 6a threshold of detection, thereby allowing foraccurate determination of the direction of the deviation vector. Forexample, one can effect a linear regression of the measurement pointsfrom the 60 threshold of detection to the distance where residuals startexceeding 6a. For further results, one can also calculate an anglebetween X-axis and the directional vector of the deviation based onregression coefficients, which angle was found to be about 74.4° forpotassium chloride under the conditions of this experiment.

The bolus of saline-diluted magnesium sulfate (MgSO4) injected into thesaline flow through the injection port was also detected by the sensor,resulting in a 2-dimensional characteristic signature of the MgSO4component—which was readily distinguishable from the signature for theKCl component. (See FIG. 9A) Multiple injections of magnesium sulfate(MgSO4) resulted in distinct substantially overlapping curves, as shown.Without being bound by theory not expressly recited in the claims, thesaline-diluted magnesium sulfate results in a unique characteristicsignature which was differentiated from the data resulting from thepotassium chloride. As seen in FIG. 9A, the deviation from the salinepoint is relatively more vertical and of a relatively smaller magnitudeas compared to the deviation of potassium chloride. The angle of theinitial deviation, calculated as explained above, was found to be 85.6°for the magnesium sulfate under the conditions of this experiment.

The bolus of deionized water injected into the saline flow through theinjection port was likewise detected by the sensor, resulting in a2-dimensional characteristic signature of the H₂O component—which wasreadily distinguishable from both the signature for the KCl componentand the signature of the MgSO4 component, deviating in nearly theopposite direction therefrom. (See FIG. 9B) The angle of initialdeviation for the water component as detected by the sensor was −118.2°.

In each case, the statistical uncertainty for the determined angles wasestimated from the residuals of the linear regression used to calculatecoefficients determining the angles, and for all threesubstances—potassium chloride, magnesium sulfide and water—was found tobe 0.62°.

These data demonstrate that highly diluted components injected intosaline flow can be identified. Generally, deviation distance from a datapoint corresponding to pure saline depends on both concentration andmolecular or ionic composition of the component, while deviationdirection from such data point depends predominantly on the molecular orionic composition of the component. For higher concentrations of thecomponent, both magnitude and direction of the deviation becomeconcentration-dependent in unique and distinguishable manner which isspecific to and dependent upon the particular component added to thesaline. Hence, such deviation dependencies enable identification ofcomponents having different compositions or concentrations.

Software can be used to identify potassium chloride, magnesium sulfideand water components within an intravenous saline fluid, based on theresults of the afore-described experimental data. In one approach, forexample, pattern recognition software can continuously observe voltagedata derived from the sensor and check whether the value exceeds the 6athreshold. Once the threshold is exceeded, the software can indicatethat a different substance is likely present in the flow and can start alinear regression on the consecutively measured points, checking whetherresiduals exceed the 6a threshold. The algorithm may, at that point,conclude that the linear section of the deviation curve was over, andmay calculate a directional vector for the data set being reduced. Thedirectional vector can be compared to vector values previouslydetermined for specific components (e.g., pharmaceuticals) of interest.More specifically, for example, such analysis can be effected in termsof angles. For example, when the detected deviation corresponds to anangle of 74.4±0.62°—the software can identify the injected bolus aslikely being potassium chloride. Similarly, for example, if the detecteddeviation corresponds to an angle of 85.6±0.62° or an angle of−118.20.62°, the software can identify injected substance as magnesiumsulfate or deionized water, respectively. If the detected deviationangle does not correspond to angle for any known substances under theconditions of measurement, then the algorithm can report a detectedunknown substance. Once a component is identified, a current cumulativedosing level can be measured by integrating either x or y or |Δx+/Δy|over time during the period defined from when the signal exceeded thedetection threshold to the current time (e.g., taking into account thesensor sensitivity to identified substance and the volumetric flow).

Such pattern recognition algorithm can also be adapted to recognizeother substances that are components of an intravenous fluid. Suchsubstances will produce deviations in various directions, the angles foreach of which can be determined as described above. In subsequentoperation, such software can compare measured angles determined fromdetected data with the values for expected angles corresponding tocertain substances, thereby identifying the substances. More elaboratepattern recognition algorithms can also be applied to thedifferentiation and recognition of data generated by the sensors inmultidimensional space, as described in the specification. The variousexamples described herein are representative of, and not to beconsidered limiting of the inventions disclosed and claimed herein.

Tables 4A, 4B and 4C follow:

TABLE 4A Heparin Dilution Series Heparin Relative Cone. Optic Admitt.Admitt* 1.000 2.1284 33.68978 14.12309 0.504 2.1390 29.85923 13.557840.248 2.1455 29.57476 13.1181  0.124, 2.1432 26.91454 13.59039 0.0002.1434 23.98381 10.90867

TABLE 4B Insulin Dilution Series Insulin Relative Cone. Optic Admitt.Admitt.* 1.000 2.1313 6.59935 1.33295 0.503 2.1402 10.9246 3.14695 0.2402.1424 17.6113 7.30539 0.126 2.1434 21.2221 10.3648 0.000 2.1434 23.983810.9087

TABLE 4C Potassium Chloride Dilution Series KCL Relative Conc. OpticAdmitt. Admitt.* 1.000 2.0889 66.51804 57.43262 0.496 2.2158 54.1641239.15326 0.221 2.1360 42.24291 27.72464 0.123 2.1420 36.42675 20.275080.000 2.1434 23.98381 10.90867

What is claimed is:
 1. A multi-parametric intravenous fluid monitoringapparatus for determining the composition of an intravenous fluid, theapparatus comprising: a substrate adapted for fluidic interface withsource of intravenous fluid prepared for delivery into a patient; afirst sensor element on the substrate comprising a pair of electrodesconfigured to measure the complex admittance or impedance of theintravenous fluid between them; a second sensor element; and a processorconfigured to receive data from the first sensor element and the secondsensor element, wherein the processor comprises a comparator configuredto compare parameters derived from the first and second sensor elementwith stored expected parameter values to identify and determine theconcentration of one or more components of the intravenous fluid.
 2. Theapparatus of claim 1, wherein the second sensor element is configured toprovide the processor with a parameter that is independent of theparameter provided by the first sensor element.
 3. The apparatus ofclaim 1, wherein the second sensor element comprises an optical element.4. The apparatus of claim 1, wherein the first sensor element comprisesan electrical admittance or impedance sensor configured to determine thecomplex admittance or impedance over a range of frequencies.
 5. Theapparatus of claim 1, wherein the second sensor element is configured tomeasure a complex admittance or impedance from the intravenous fluid andcomprises at least one electrode separate from the pair of electrodes ofthe first sensor element.
 6. The apparatus of claim 1, wherein theprocessor comprises stored expected parameter values able to uniquelyidentify one or more pharmaceuticals in a carrier solution, wherein thecarrier solution comprises one of: D5W, 3.3% Dextrose/0.3% saline,Half-normal saline, Normal saline, and Ringers lactate, and the one ormore pharmaceuticals comprises one or more of: an anticoagulant, ametabolically-active hormone, an anticoagulant, and an analgesic.
 7. Amulti-parametric intravenous fluid monitoring apparatus for determiningthe composition of an intravenous fluid, the apparatus comprising: asubstrate adapted for fluidic interface with source of intravenous fluidprepared for delivery into a patient; a first sensor element on thesubstrate comprising a first electrode and a second electrode, the firstsensor element configured to measure a first complex admittance orimpedance of the intravenous fluid between the first and secondelectrodes; a second sensor element on the substrate comprising a thirdelectrode formed of a different conductive material than the first andsecond electrodes, the second sensor element configured to measure asecond complex admittance or impedance of the intravenous fluid betweenthe third electrode and another electrode; and a processor configured toreceive complex admittance or impedance data from the first sensorelement and the second sensor element, wherein the processor comprises acomparator configured to compare parameters derived from the first andsecond sensor elements with stored expected parameter values to identifyand determine the concentration of one or more components of theintravenous fluid.
 8. The apparatus of claim 7, wherein the first,second and third electrodes are each formed of a conductive materialselected from the group consisting of: Au, Pt, Pd, Ag, W, Ti, Ni, Sn,and Co.
 9. The apparatus of claim 7, wherein the substrate is within ahousing comprising one or more conduits and having a first end adaptedfor fluid communication with the fluid source and a second end adaptedfor fluid communication with an intravenous infusion device for infusionof fluid into the vascular system of the patient.
 10. The apparatus ofclaim 7, wherein the second sensor element comprises the third electrodeand one of the first or second electrodes from the first sensor element.11. The apparatus of claim 7, further comprising a third sensor element,further wherein the processor is configured to receive and compare datafrom the third sensor element to identify and determine theconcentration of one or more component of the intravenous fluid.
 12. Theapparatus of claim 7, further comprising an optical sensor element. 13.The apparatus of claim 7, wherein the first sensor element comprises anadmittance or impedance sensor configured to determine complexadmittance or impedance at a plurality of frequencies.
 14. The apparatusof claim 7, wherein the second sensor element comprises an admittance orimpedance sensor configured to determine complex admittance or impedanceat a plurality of frequencies.
 15. An intravenous fluid monitoringapparatus for determining the composition of an intravenous fluid, theapparatus comprising: a substrate adapted for fluidic interface withsource of intravenous fluid prepared for delivery into a patient; asensor element on the substrate comprising a first electrode and asecond electrode, the sensor element configured to measure a firstcomplex admittance or impedance of the intravenous fluid between thefirst and second electrodes; a processor configured to receive parametervalues incorporating the complex admittance or impedance data from thesensor element, wherein the processor comprises a comparator configuredto compare the received parameter values with stored expected parametervalues to identify and determine the concentration of components of theintravenous fluid.
 16. The apparatus of claim 15, wherein the first andsecond electrodes are formed of different conductive materials.
 17. Theapparatus of claim 15, wherein the first and second electrodes are eachformed of a conductive material selected from the group consisting of:Au, Pt, Pd, Ag, W, Ti, Ni, Sn, and Co.
 18. The apparatus of claim 15,wherein the substrate is within a housing comprising one or moreconduits and having a first end adapted for fluid communication with thefluid source and a second end adapted for fluid communication with anintravenous infusion device for infusion of fluid into the vascularsystem of the patient.
 19. The apparatus of claim 15, further comprisinga second sensor element on the substrate, the second sensor elementcomprising a third electrode, the second sensor element configured tomeasure a first complex admittance or impedance of the intravenous fluidbetween the third electrode and another electrode.
 20. The apparatus ofclaim 19, wherein the second sensor element comprises the thirdelectrode and another electrode selected from either the first electrodeor the second electrode of the first sensor element.
 21. The apparatusof claim 15, wherein the sensor element comprises an admittance orimpedance spectroscopy sensor configured to determine complex admittanceor impedance at a plurality of frequencies.